Allo‐cross‐reactivity of a human neuraminidase‐specific T cell clone dependent on presentation of an endogenous B cell‐specific antigen

T cell specific for foreign antigen recognize a complex of peptides and self‐major histocompatibility complex (MHC) molecules and can also cross‐react with allo‐MHC molecules. It remains controversial, however, what alloreactive T cells exactly recognize. It has been proposed that alloreactive T cells recognize endogenous peptides presented by allo‐MHC molecules. To test this hypothesis, we examined an influenza virus‐specific T cell clone (6H5), specific for neuraminidase N2 and restricted by HLA‐DR1. In the absence of influenza virus, this clone cross‐reacted with HLA‐DR1Dw1+ but not with HLA‐DR1Dw20+ Epstein‐Barr virus‐transformed lymphoblastoid cells (B‐LCL). Cold target inhibition experiments and the rearrangement pattern of the T cell receptor β chain indicated that 6H5 was a monoclonal T cell population most likely using the same T cell receptor for both responses. To determine whether determinants other than HLA‐DR1Dw1 itself were involved in the allorecognition of 6H5, this clone was tested on several cell types. In the absence of virus, T cell clone 6H5 responded to HLA‐DR1Dw1+ B‐LCL or activated B cells, but, surprisingly, not to other cell types expressed HLA‐DR1Dw1, including monocytes and transfected L cells. These experiments further support the concept that recognition of allogeneic MHC (in this case HLA‐DR1Dw1) may result from a cross‐reactivity of T cells specific for a complex of foreign antigen and self‐MHC (neuraminidase N2 and HLA‐DR1Dw20). Furthermore, allorecognition of T cell clone 6H5 appears to depend upon the recognition of a complex of allogeneic MHC and a cell‐type specific endogenous peptide presented by activated B cells.