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J Biol Chem, Vol. 274, Issue 49, 35119-35128, December 3, 1999

Conformational and Biochemical Differences in the TCR·CD3 Complex of CD8⁺ Versus CD4⁺ Mature Lymphocytes Revealed in the Absence of CD3

David A. Zapata, Alberto Pacheco-Castro, Pilar S. Torres, Almudena R. Ramiro^**, Ester San José^**, Balbino Alarcón^**, Laeticia Alibaud, Bent Rubin, María L. Toribio^**, and José R. Regueiro

From  Inmunología, Facultad de Medicina, Universidad Complutense, 28040 Madrid, Spain, the ^** Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Cientificas, Facultad de Biología, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain, and the  Centre d'Immunopathologie et de Génétique Humaine, Centre National de la Recherche Scientifique, Centre Hospitalaire Universitaire de Purpan, 31300 Toulouse, France

Mature CD4⁺ and CD8⁺ T lymphocytes are believed to build and express essentially identical surface T-cell receptor-CD3 (TCR·CD3) complexes. However, TCR·CD3 expression has been shown to be more impaired in CD8⁺ cells than in CD4⁺ cells when CD3 is absent in humans or mice. We have addressed this paradox by performing a detailed phenotypical and biochemical analysis of the TCR·CD3 complex in human CD3-deficient CD8⁺ and 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. In addition, CD8⁺, but not CD4⁺, CD3-deficient T lymphocytes were shown to contain abnormally glycosylated TCR proteins, together with a smaller, abnormal TCR chain (probably incompletely processed TCR). These results suggest the existence of hitherto unrecognized biochemical differences between mature CD4⁺ and CD8⁺ T lymphocytes in the intracellular control of TCR·CD3 assembly, maturation, or transport that are revealed when CD3 is absent. Such lineage-specific differences may be important in receptor-coreceptor interactions during antigen recognition.

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