Abstract:
:The discovery that genes in the major histocompatibility complex (MHC) play an important role in the immune response depended on the chance interaction of several unrelated events. The first, and most important, was the decision by Michael Sela to synthesize a series of branched, multichain, synthetic polypeptides based on a backbone of poly-l-lysine. The prototype compound, (T,G)-A-L, was tipped with short random sequences of tyrosine and glutamic acid. This resulted in a restricted range of antigenic determinants composed of only two or three amino acids with a variable length-ideal for binding to the peptide binding groove of MHC class II molecules. The second was the decision by John Humphrey to immunize various strains of rabbits with this synthetic polypeptide. Two of these rabbit strains showed very large quantitative differences in antibody response to (T, G)-A-L. In transferring this system to inbred mouse strains, the third bit of good fortune was the availability at the National Institute of Medical Research, in Mill Hill (London), of the CBA (H2(k)) and C57 (H2(b)) strains. The H2(b) haplotype is the only one mediating a uniform high antibody response to (T,G)-A-L. The fourth critical ingredient was the availability of numerous congenic and H2 recombinant inbred strains of mice produced earlier by Snell, Stimpfling, Shreffler, and Klein. A search for congenic pairs of mice expressing the responder and nonresponder H2 haplotypes on the same background revealed that these strains responded as a function of their H2 haplotype, not of their inbred background. Extensive studies in a variety of inbred strains carrying recombinant H2 haplotypes, as well as a four-point linkage cross, mapped immune response to (T,G)A-L within the murine MHC, between the K and Ss loci. The demonstration that stimulation in the mixed lymphocyte reaction (MLR) mapped to the same region quickly led to attempts to produce antisera in congenic H2 recombinant strain combinations. These antisera identified I-region associated (Ia) antigens. Immunoprecipitation and blocking studies showed that the gene products controlling specific immune responses, the mixed lymphocyte reaction, and the structure of Ia antigens were one and the same-now designated as the I-A MHC class II molecules. These antisera and inbred strains enabled Unanue to demonstrate the peptide binding function of class II MHC molecules.
journal_name
Annu Rev Immunoljournal_title
Annual review of immunologyauthors
McDevitt HOdoi
10.1146/annurev.immunol.18.1.1subject
Has Abstractpub_date
2000-01-01 00:00:00pages
1-17eissn
0732-0582issn
1545-3278pii
18/1/1journal_volume
18pub_type
杂志文章,评审abstract::The bare lymphocyte syndrome (BLS) is a hereditary immunodeficiency resulting from the absence of major histocompatibility complex class II (MHCII) expression. Considering the central role of MHCII molecules in the development and activation of CD4(+) T cells, it is not surprising that the immune system of the patient...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.19.1.331
更新日期:2001-01-01 00:00:00
abstract::Licensed vaccines against viral diseases generate antibodies that neutralize the infecting virus and protect against infection or disease. Similarly, an effective vaccine against HIV-1 will likely need to induce antibodies that prevent initial infection of host cells or that limit early events of viral dissemination. ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-030409-101256
更新日期:2010-01-01 00:00:00
abstract::T cell development involves stepwise progression through defined stages that give rise to multiple T cell subtypes, and this is accompanied by the establishment of stage-specific gene expression. Changes in chromatin accessibility and chromatin modifications accompany changes in gene expression during T cell developme...
journal_title:Annual review of immunology
pub_type: 杂志文章
doi:10.1146/annurev-immunol-092719-082622
更新日期:2020-04-26 00:00:00
abstract::The immune system is composed of single cells, and its function is entirely dependent on the capacity of these cells to traffic, localize within tissues, and interact with each other in a precisely coordinated fashion. There is growing evidence that the large families of chemokines and chemokine receptors provide a fl...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.18.1.593
更新日期:2000-01-01 00:00:00
abstract::During the last decade the immunoglobulin J chain has indeed come of age. The amino-acid sequence has been determined for the mouse and human polypeptides, and the data obtained have established the uniqueness of the primary structure and its high degree of conservation in vertebrates. The biosynthesis of J chain has ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.03.040185.002233
更新日期:1985-01-01 00:00:00
abstract::The presence of intestinal intra-epithelial lymphocytes (IEL) has been appreciated for over 100 years. However, until recently, the IEL were thought to be simply another specialized component of the gut-associated lymphoid tissue (GALT), sharing the same origin as lymphocytes found in other GALT compartments such as t...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.12.040194.002513
更新日期:1994-01-01 00:00:00
abstract::The diverse microbial populations constituting the intestinal microbiota promote immune development and differentiation, but because of their complex metabolic requirements and the consequent difficulty culturing them, they remained, until recently, largely uncharacterized and mysterious. In the last decade, deep nucl...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-032713-120238
更新日期:2015-01-01 00:00:00
abstract::Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflamma...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-032713-120252
更新日期:2015-01-01 00:00:00
abstract::Chemokines are chemotactic cytokines that control the migratory patterns and positioning of all immune cells. Although chemokines were initially appreciated as important mediators of acute inflammation, we now know that this complex system of approximately 50 endogenous chemokine ligands and 20 G protein-coupled seven...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-032713-120145
更新日期:2014-01-01 00:00:00
abstract::Gene-chips contain thousands of nucleotide sequences that allow simultaneous analysis of the complex mixture of RNAs transcribed in cells. Like these gene-chips, major histocompatibility complex (MHC) class I molecules display a large array of peptides on the cell surface for probing by the CD8(+) T cell repertoire. T...
journal_title:Annual review of immunology
pub_type: 杂志文章
doi:10.1146/annurev.immunol.20.100301.064819
更新日期:2002-01-01 00:00:00
abstract::Sialic acid-binding immunoglobulin-type lectins (Siglecs) are expressed on the majority of white blood cells of the immune system and play critical roles in immune cell signaling. Through recognition of sialic acid-containing glycans as ligands, they help the immune system distinguish between self and nonself. Because...
journal_title:Annual review of immunology
pub_type: 杂志文章
doi:10.1146/annurev-immunol-102419-035900
更新日期:2020-04-26 00:00:00
abstract::The transmembrane receptor Notch participates in diverse cell fate decisions throughout embryonic development. Notch receptors and their ligands are expressed in the mammalian thymus, raising the possibility that Notch could regulate T cell fate decisions. Expression of a constitutively activated form of Notch in deve...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.17.1.283
更新日期:1999-01-01 00:00:00
abstract::The discovery of tissue-resident innate lymphoid cell populations effecting different forms of type 1, 2, and 3 immunity; tissue repair; and immune regulation has transformed our understanding of mucosal immunity and allergy. The emerging complexity of these populations along with compounding issues of redundancy and ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-041015-055549
更新日期:2016-05-20 00:00:00
abstract::This article outlines my early start in medicine, a late start in immunology research, and my efforts to integrate the two activities. I first describe some of the background information, excitement, and implications of the recognition of T and B cells as separate but functionally intertwined arms of the adaptive immu...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-030409-101248
更新日期:2010-01-01 00:00:00
abstract::Over the past decade, key protein interactions contributing to T cell antigen recognition have been characterized in molecular detail. These have included interactions involving the T cell antigen receptor (TCR) itself, its coreceptors CD4 and CD8, the accessory molecule CD2, and the costimulatory receptors CD28 and C...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.21.120601.141036
更新日期:2003-01-01 00:00:00
abstract::The gut-associated lymphoid tissue (GALT) faces a considerable challenge. It encounters antigens derived from an estimated 1014 commensal microbes and greater than 30 kg of food proteins yearly. It must distinguish these harmless antigens from potential pathogens and mount the appropriate host immune response. Local a...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-042718-041621
更新日期:2019-04-26 00:00:00
abstract::The complement system is an evolutionarily ancient key component of innate immunity required for the detection and removal of invading pathogens. It was discovered more than 100 years ago and was originally defined as a liver-derived, blood-circulating sentinel system that classically mediates the opsonization and lyt...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-042617-053245
更新日期:2018-04-26 00:00:00
abstract::The current status of T-cell subset involvement in viral immunity is summarized for experimental studies in mice. The immunobiology of the normal host response is discussed, with particular reference to lymphocytic choriomeningitis (LCM) and influenza. The general impression is that CD8+ cytotoxic T lymphocytes, CD4+ ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.10.040192.001011
更新日期:1992-01-01 00:00:00
abstract::T helper cell differentiation occurs in the context of the extracellular cytokine milieu evoked by diverse microbes and other pathogenic stimuli along with T cell receptor stimulation. The culmination of these signals results in specification of T helper lineages, which occurs through the combinatorial action of multi...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-020711-075058
更新日期:2012-01-01 00:00:00
abstract::The discovery of new functions for the original B7 family members, together with the identification of additional B7 and CD28 family members, have revealed new ways in which the B7:CD28 family regulates T cell activation and tolerance. B7-1/B7-2:CD28 interactions not only promote initial T cell activation but also reg...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.23.021704.115611
更新日期:2005-01-01 00:00:00
abstract::T cell anergy is a tolerance mechanism in which the lymphocyte is intrinsically functionally inactivated following an antigen encounter, but remains alive for an extended period of time in a hyporesponsive state. Models of T cell anergy affecting both CD4(+) and CD8(+) cells fall into two broad categories. One, clonal...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.21.120601.141110
更新日期:2003-01-01 00:00:00
abstract::Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimeric antigen receptor (CAR) T cells were recently approved by the US Food and Drug Administration and are poised to enter the practice of medicine for leukemia and lymphoma, demonstrating that e...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-042718-041407
更新日期:2019-04-26 00:00:00
abstract::Autoimmunity and the pathogenesis of autoimmune diseases were a major focus of the Walter and Eliza Hall Institute, where I started my research career. After my initial studies on immune cell culture and immune regulation, I returned to an analysis of the pathogenesis of human autoimmunity in London. Linking upregulat...
journal_title:Annual review of immunology
pub_type: 传,历史文章,杂志文章
doi:10.1146/annurev-immunol-082708-100732
更新日期:2009-01-01 00:00:00
abstract::In contrast to T cell receptors, signal transducing cell surface membrane molecules involved in the regulation of responses by cells of the innate immune system employ structures that are encoded in the genome rather than generated by somatic recombination and that recognize either classical MHC-I molecules or their s...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.20.100301.064812
更新日期:2002-01-01 00:00:00
abstract::T and B cells share a common somatic gene rearrangement mechanism for assembling the genes that code for their antigen receptors; they also have developmental pathways with many parallels. Shared usage of basic helix-loop-helix E proteins as transcriptional drivers underlies these common features. However, the transcr...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-032712-100024
更新日期:2014-01-01 00:00:00
abstract::The introduction of cloned genes into the germline of mice has been proven to be a powerful tool to investigate the role of the respective gene products within the immune system. Here we summarize the transgenic mouse models that have been established with major histocompatibility complex (MHC) class-I genes. Foreign ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.09.040191.001501
更新日期:1991-01-01 00:00:00
abstract::During alphabeta T cell development, cells diverge into alternate CD4 helper and CD8(+) cytotoxic T cell lineages. The precise correlation between a T cell's CD8 and CD4 choice and its TCR specificity to class I or class II MHC was noted more than 20 years ago, and establishing the underlying mechanism has remained a ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.25.022106.141715
更新日期:2010-01-01 00:00:00
abstract::In light of recent data showing that both helper and cytotoxic T cells can detect even a single molecule of an agonist peptide-MHC, alphabeta T cells are clearly a type of sensory cell, comparable to any in the nervous system. In addition, endogenous (self) peptides bound to MHCs are not just important for thymic sele...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.24.021605.090600
更新日期:2007-01-01 00:00:00
abstract::The transcription factor NF-kappa B, more than a decade after its discovery, remains an exciting and active area of study. The involvement of NF-kappa B in the expression of numerous cytokines and adhesion molecules has supported its role as an evolutionarily conserved coordinating element in the organism's response t...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.16.1.225
更新日期:1998-01-01 00:00:00
abstract::Adaptive immune recognition is mediated by antigen receptors on B and T cells generated by somatic recombination during lineage development. The high level of diversity resulting from this process posed technical limitations that previously limited the comprehensive analysis of adaptive immune recognition. Advances ov...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-042718-041757
更新日期:2019-04-26 00:00:00