AbstractPositive selection of T cells within the thymus gland leads to major histocompatibility complex (MHC)‐restricted recognition of antigen by T lymphocytes. As the thymus gland involutes with age, altered MHC‐restricted antigen recognition by T cells from elderly humans would be expected. We have tested this hypothesis by comparing the proliferative response of T cells and T cell clones from aged and young subjects to influenza determinants presented by autologous or allogeneic antigen‐presenting cells (APC). Under conditions in which the allogeneic mixed lymphocyte reaction was minimal, T cells from six of seven aged donors but only one of seven young donors were stimulated by influenza vaccine presented by allogeneic APC. More importantly, one‐half of the influenza‐specific T cell clones derived from aged donors, but none of the clones derived from young donors, were activated by influenza vaccine presented by allogeneic APC. While 80 of the MHC‐nonrestricted influenza‐specific T cell clones expressed the γ/δ T cell receptor, 20 of these clones expressed the α/β T cell receptor. Thus, changes in MHC‐restricted antigen recognition by T cells and in altered distribution of α/βversusthe γ/δ T cell receptor bearing antigen‐specific T cel
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