Modulation of T cell development by an endogenous altered peptide ligand - PubMed (original) (raw)

Modulation of T cell development by an endogenous altered peptide ligand

B L Hsu et al. J Exp Med. 1995.

Abstract

T cells potentially encounter numerous endogenous peptides during selection in the thymus and in the periphery. We examined the impact of an endogenous peptide on in vivo T cell development, using a TCR transgenic mouse model based on a hemoglobin-specific T cell clone. In these mice, the transgenic beta chains paired with endogenous alpha chains. This led to a serendipitous primary reactivity to Ser69 peptide, an altered peptide ligand of the Hbd (64-76) epitope of the parent clone. Two Ser69-reactive T cell populations were identified. A smaller population of the Ser69-reactive T cells responded both to Ser69 and Hbd (64-76). A majority reacted only to Ser69, and not to Hbd(64-76); in fact, Hbd(64-76) was a specific TCR antagonist for these Ser69-only-reactive T cells. Thus, in this unique experimental system, Ser69 became an agonist, and Hbd (64-76) was an antagonist. Endogenous presentation of the antagonist ligand in the thymus selectively eliminated the high-avidity cells, while sparing low-avidity cells in the Ser69-reactive T cell repertoire. These results highlight how specificity guides developing T cells through a network of ligands and indicate that the endogenous peptide pool has a profound effect on T cell development and repertoire.

PubMed Disclaimer

References

    1. J Exp Med. 1994 May 1;179(5):1539-49 -PubMed
    1. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2300-4 -PubMed
    1. J Exp Med. 1994 Oct 1;180(4):1195-205 -PubMed
    1. Immunol Rev. 1988 Jan;101:149-72 -PubMed
    1. Immunol Rev. 1988 Jan;101:173-90 -PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources