Identification of the ligand recognized by a mAb specific for CD4^+CD8^+ thymocyte

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Although the diversity of αβ T cell receptors (TCRs) theoretically reaches 10^<15> by random rearrangement of five gene segments and random nucleotide addition, mature T cells express highly selected TCRs in that they exhibit tolerance to self-antigenic peptides and restriction by self-MHC molecules. This mainly results from two reciprocal selection processes, positive and negative selection, acting at CD4^+CD8^+ stage during T cell development in the thymus. With the use of the mAb specific for CD4^+CD8^+ thymocytes, we found that CD4^+CD8^+ thymocytes lacking TCR- MHC/peptide complex interaction specifically express multimerized Thy1 molecules. On the other hand, we developed several transgenic-knockout mouse lines expressing distinct peptides as a single species. By comparing T cell differentiation among these mice, we found positive selection is both specific and degenerate, dependending on the amino acid residues at TCR contacts of the selecting self-peptides.