T cell receptor interactions with class I heavy-chain influence T cell selection

The interaction of the T cell receptor (TCR) with peptide in the binding si te of the major histocompatibility complex molecule provides the basis for T cell recognition during immune surveillance, repertoire development, and tolerance. Little is known about the extent to which repertoire selection i s influenced directly by variation of the structure of the class I heavy ch ain. We find that the 2C TCR, normally positively selected in the context o f the K-b molecule, is minimally selected into the CD8 lineage in the absen ce of antigen-processing genes. This finding underscores the importance of peptides in determining the positive-selecting class I ligands in the thymu s. In contrast, K-bm3, a valiant class I molecule that normally exerts a ne gative selection pressure on 2C-bearing T cells, positively selects 2C tran sgenic T cells into the CD8 lineage in an antigen-processing gene-deficient environment. These findings indicate that structural changes in the heavy chain can have direct influence in T cell recognition, from which we conclu de that the nature of TCR interaction with class I heavy chain influences t he array of TCRs selected during development of the functional adult repert oire.