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The role of MHC class I allele Mamu-A*07 during SIV(mac)239 infection.

Abstract：

:Virus-specific CD8(+) T cells play an important role in controlling HIV/SIV replication. These T cells recognize intracellular pathogen-derived peptides displayed on the cell surface by individual MHC class I molecules. In the SIV-infected rhesus macaque model, five Mamu class I alleles have been thoroughly characterized with regard to peptide binding, and a sixth was shown to be uninvolved. In this study, we describe the peptide binding of Mamu-A1*007:01 (formerly Mamu-A*07), an allele present in roughly 5.08% of Indian-origin rhesus macaques (n = 63 of 1,240). We determined a preliminary binding motif by eluting and sequencing endogenously bound ligands. Subsequently, we used a positional scanning combinatorial library and panels of single amino acid substitution analogs to further characterize peptide binding of this allele and derive a quantitative motif. Using this motif, we selected and tested 200 peptides derived from SIV(mac)239 for their capacity to bind Mamu-A1*007:01; 33 were found to bind with an affinity of 500 nM or better. We then used PBMC from SIV-infected or vaccinated but uninfected, A1*007:01-positive rhesus macaques in IFN-γ Elispot assays to screen the peptides for T-cell reactivity. In all, 11 of the peptides elicited IFN-γ(+) T-cell responses. Six represent novel A1*007:01-restricted epitopes. Furthermore, both Sanger and ultradeep pyrosequencing demonstrated the accumulation of amino acid substitutions within four of these six regions, suggestive of selective pressure on the virus by antigen-specific CD8(+) T cells. Thus, it appears that Mamu-A1*007:01 presents SIV-derived peptides to antigen-specific CD8(+) T cells and is part of the immune response to SIV(mac)239.

journal_name

Immunogenetics

journal_title

Immunogenetics

authors

Reed JS,Sidney J,Piaskowski SM,Glidden CE,León EJ,Burwitz BJ,Kolar HL,Eernisse CM,Furlott JR,Maness NJ,Walsh AD,Rudersdorf RA,Bardet W,McMurtrey CP,O'Connor DH,Hildebrand WH,Sette A,Watkins DI,Wilson NA

doi

10.1007/s00251-011-0541-9

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

789-807

issue

12

eissn

0093-7711

issn

1432-1211

journal_volume

63

pub_type

杂志文章

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