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Deletion of CD4 and CD8 coreceptors permits generation of alphabetaT cells that recognize antigens independently of the MHC.

Abstract：

:The thymus generates major histocompatibility complex (MHC)-restricted alphabetaT cells that only recognize antigenic ligands in association with MHC or MHC-like molecules. We hypothesized that MHC specificity might be imposed on a broader alphabetaTCR repertoire during thymic selection by CD4 and CD8 coreceptors that bind and effectively sequester the tyrosine kinase Lck, thereby preventing T cell receptor (TCR) signaling by non-MHC ligands that do not engage either coreceptor. This hypothesis predicts that, in coreceptor-deficient mice, alphabeta thymocytes would be signaled by non-MHC ligands to differentiate into alphabetaT cells lacking MHC specificity. We now report that MHC-independent alphabetaT cells were indeed generated in mice deficient in both coreceptors as well as MHC ("quad-deficient" mice) and that such mice contained a diverse alphabetaT cell repertoire whose MHC independence was confirmed at the clonal level. We conclude that CD4 and CD8 coreceptors impose MHC specificity on a broader alphabetaTCR repertoire during thymic selection by preventing thymocytes from being signaled by non-MHC ligands.

journal_name

Immunity

journal_title

Immunity

authors

Van Laethem F,Sarafova SD,Park JH,Tai X,Pobezinsky L,Guinter TI,Adoro S,Adams A,Sharrow SO,Feigenbaum L,Singer A

doi

10.1016/j.immuni.2007.10.007

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

735-50

issue

5

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(07)00491-8

journal_volume

27

pub_type

杂志文章

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