Conformational and biochemical differences in the TCR center dot CD3 complex of CD8(+) versus CD4(+) mature lymphocytes revealed in the absence of CD3 gamma

Mature CD4(+) and CD8(+) T lymphocytes are believed to build and express es sentially identical surface alpha beta T-cell receptor-CD3 (TCR.CD3) comple xes, However, TCR.CD3 expression has been shown to be more impaired in CD8( +) cells than in CD4(+) cells when CD3 gamma is absent in humans or mice. W e have addressed this paradox by performing a detailed phenotypical and bio chemical analysis of the TCR.CD3 complex in human CD3 gamma-deficient CD8and CD4(+) T cells. The results indicated that the membrane TCR.CD3 complex of CD8(+) T lymphocytes was conformationally different from that of CD4(+) lymphocytes in the absence of CD3 gamma, In addition, CD8(+), but not CD4( +), CD3 gamma-deficient T lymphocytes were shown to contain abnormally glyc osylated TCR beta proteins, together with a smaller, abnormal TCR chain (pr obably incompletely processed TCR alpha), These results suggest the existen ce of hitherto unrecognized biochemical differences between mature CD4(+) a nd CD8(+) T lymphocytes in the intracellular control of alpha beta TCR.CD3 assembly, maturation, or transport that are revealed when CD3 gamma is abse nt, Such lineage-specific differences may be important in receptor-corecept or interactions during antigen recognition.