Dual HLA class I and class II restricted recognition of alloreactive T lymphocytes mediated by a single T cell receptor complex

The alloreactive human T cell clone MBM15 was found to exhibit dual specifi city recognizing both an antigen in the context of the HLA class I A2 molec ule and an antigen in the context of the HLA class Il DR1, We demonstrated that the dual reactivity that was mediated via a single clonal T cell popul ation depended on specific peptide binding. For complete recognition of the H LA-A2-restricted specificity the interaction of CD8 with HLA class I is essential. Interestingly, interaction of the CD8 molecule with HLA class I contributed to the HLA-DR1-restricted specificity. T cell clone MBM15 expre ssed two in-frame T cell receptor (TCR) V alpha transcripts (V alpha1 and V alpha2) and one TCR V beta transcript (V beta 13). To elucidate whether tw o TCR complexes were responsible for the dual recognition or one complex, c ytotoxic T cells were transduced with retroviral vectors encoding the diffe rent TCR chains. Only T cells transduced with the TCR V alpha 1V beta 13 co mbination specifically recognized both the HLA-A2(+) and HLA-DR1(+) target cells, whereas the V alpha 2V beta 13 combination did not result in a TCR o n the cell surface. Thus a single TCR alpha beta complex can have dual spec ificity, recognizing both a peptide in the context of HLA class I as well a s a peptide in the context of HLA class II. Transactivation of T cells by a n unrelated antigen in the context of HLA class II may evoke an HLA class I -specific T cell response. We propose that this finding may have major impl ications for immunotherapeutic interventions and insight into the developme nt of autoimmune diseases.