RECOGNITION OF AN IMMUNOGLOBULIN V(H) EPITOPE BY INFLUENZA VIRUS-SPECIFIC CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX-RESTRICTED CYTOLYTIC T-LYMPHOCYTES

There are two immunogenic sites on the type A influenza A/Japan/57 (H2 N2) hemagglutinin (HA) that can be recognized by class I major histoco mpatibility complex (MHC), H-2K(d)-restricted cytolytic T lymphocytes (CTLs). One of these sites encompasses two distinct partially overlapp ing epitopes, which span HA residues 204-212 and 210-219. During the a nalysis of the fine specificity of CTL clones directed to the HA 210-2 19 epitope, we found that one clone 40-2 also recognized the myeloma c ell line P3x63-Ag8. P3x63-Ag8 is derived from the MOPC 21 myeloma and expresses an immunoglobulin (Ig) heavy chain variable region (V-H) gen e which is a member of the murine 7183 V-H gene family. Recognition wa s specific for the endogenously processed MOPC 21 heavy chain in assoc iation with the K-d molecules, since the SP2/0 derivative of P3x63-Ag8 , which does not make a functional Ig H chain, is not recognized. The V-H epitope recognized by clone 40-2 could be mapped to a 10 amino aci d peptide spanning MOPC 21 V-H residues 49-58. Cross-reactivity for th e V-H gene product was also demonstrable in some heterogeneous populat ions of CTL generated in response to influenza virus infection. These results represent the first demonstration of cross-reactivity for an e ndogenously processed product of a self-Ig by the CTL directed to a fo reign antigen and raise the possibility that the Ig V-H expression may regulate the CD8(+) T cell response to foreign antigens.