When examining the effects of peptide analogues without proliferation-inducing activity on three human CD4+ T cell clones with distinct TCRbeta recognizing a nonself mycobacterial bacillus Calmette-Guerin a (BCGa) peptide fragment (EEYLILSARDVLAVVSK)/HLA-DR14 complex, we found that 1) stimulation of T cells with a one-residue-substituted analogue or a minimally homologous self peptide fragment derived from human connexin 26 (IMILVVAAKEVWGDEQA) can prolong the in vitro survival of T cells, in a clone specific-manner; 2) this prolongation is associated with the up-regulation of Bcl-xL without proliferation; and 3) these peptide-clone combinations are capable of inducing lymphokine secretion. Thus, peptide partial agonism may play a role in the survival of not only thymocytes but also mature T cells, in the absence of wild-type ligands.

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