T cells specific for viral antigens presented by HLA-Dw4 recognize DR13 on allogeneic cells: a possible mechanism for induction of rejection

Abstract

Alloreactivity probably involves T cell recognition of peptides bound to allogeneic HLA molecules. In order to study whether T cells recognizing common viral antigens presented by self HLA molecules also recognize some allogeneic HLA molecules we generated T lymphocyte clones (TLC) specific for herpes simplex virus (HSV) antigen. Two TLC were found which recognized HSV presented by self Dw4, but which also respond to DR13 on allogeneic cells in the absence of HSV. The response against DR13 could be inhibited by preincubating the allogeneic cells with tetanus toxoid, but not with other protein antigens tested. The difference between Dw4 (encoded by DRB1*0401) and DR13 (encoded by DRB1*1302) mainly involves amino acid residues assumed to be of importance for peptide binding, and not residues putatively interacting with the T cell receptor. Thus, the results suggest that T cells recognizing a virally-derived peptide presented by self Dw4 molecules may also recognize a different peptide presented by allogeneic DR13 molecules. Our findings indicate that some rejection episodes may be induced and effected by T cells activated by viral peptides presented by self HLA molecules.