PEPTIDE VARIABILITY EXISTS WITHIN a AND a SUBUNITS OF THE T CELL RECEPTOR FOR ANTIGEN BY ORESTE ACUTO , * STEFAN C . MEUER , JAMES C . HODGDON , STUART F . SCHLOSSMAN , AND ELLIS

To identify the antigen receptor on human T lymphocytes, clonal T cell populations of predefined specificities were utilized as immunogens for monoclonal antibody generation . Two sets of clonally unique (clonotypic) monoclonal antibodies resulted (1, 2) . The first defined a surface molecule (Ti t ) on an MHC class I-specific cytolytic T lymphocyte (CTL) clone termed CT8111 (1), whereas the second defined a clonotypic structure (Ti2) on an MHC class II-specific CTL clone termed CT4 (2). The Ti, and Ti2 structures were both 90-kdalton heterodimers composed of disulfide-linked 49-51-kdalton a and 43-kdalton 0 subunits (2) . These in turn were noncovalently associated on the membrane with the monomorphic T3 molecule . It is likely that Ti, and Ti2 represent the antigen receptor on CT811 , and CT411 , respectively since triggering with the relevant anti-Ti monoclonal antibody resulted in specific clonal proliferation and lymphokine production analogous to stimulation by antigen itself (3) . Although Ti, and Ti2 are comparable in molecular characteristics andderived from T cells of the same individual, they express unique epitopes that can be detected by the above non-cross-reactive monoclonal antibodies (2). To define the structural basis for these differences, comparative biochemical analysis of the individual subunits of the Ti, and Ti2 molecules was carried out. The results demonstrate that each subunit has a distinct pl . More importantly, 2-D peptide map comparison of Ti, and Ti2 a chains, as well as the Ti t and Ti2 ,Q chains, indicates that they are comprised of both common and unique peptide fragments.