Abstract
Mature CD4(+) and CD8(+) T lymphocytes are believed to build and express essentially identical surface alphabeta 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 CD3gamma 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 CD3gamma-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 CD3gamma. In addition, CD8(+), but not CD4(+), CD3gamma-deficient T lymphocytes were shown to contain abnormally glycosylated TCRbeta proteins, together with a smaller, abnormal TCR chain (probably incompletely processed TCRalpha). These results suggest the existence of hitherto unrecognized biochemical differences between mature CD4(+) and CD8(+) T lymphocytes in the intracellular control of alphabetaTCR. CD3 assembly, maturation, or transport that are revealed when CD3gamma is absent. Such lineage-specific differences may be important in receptor-coreceptor interactions during antigen recognition.
Highlights
Mature ␣ T lymphocytes recognize pathogen-derived peptides on antigen-presenting cells by means of the multimeric membrane protein ensemble termed the T-cell receptor (TCR)11⁄7CD3 complex
The recent availability of Herpesvirus saimiri C-488 (HVS)immortalized mature peripheral CD3␥-deficient CD8ϩ lymphocytes [5] has allowed us to address this paradox in the case of human CD3␥ deficiency, by studying phenotypically and biochemically the TCR1⁄7CD3 complex of human CD3␥-deficient CD8ϩ T cells in comparison with CD4ϩ T cells lacking CD3␥ and with appropriate ␥-sufficient controls
Peripheral Blood CD8ϩ Lymphocytes from a Human CD3␥ Deficiency Were Functional T Cells with a Normal V Repertoire—The barely detectable surface expression of certain TCR1⁄7CD3 epitopes in CD8ϩ lymphocytes from human CD3␥ deficiency (Fig. 1A and Ref. 4), together with the fact that they did not grow in optimal T-cell culture conditions [4], could be interpreted as an indication that they were not T lymphocytes at all but rather NK-lineage cells
Summary
T-Cell Sciences, Cambridge, MA [13] O. Institut Pasteur, Paris, France [14] Endogene, Woburn, MA Becton Dickinson, Mountain View, CA Ortho Diagnostic, Raritan, NJ Caltag, Burlingame, CA T-Cell Sciences B. Centro de Biologıa Molecular Severo Ochoa, Madrid, Spain E. E. de Vries, The Netherlands Cancer Institute, Amsterdam, The Netherlands R. Centre Regional de Transfusion Sanguine, Rennes, France B. Centre Hospitaliare Universitaire de Purpan, Toulouse, France B. Centro de Biologıa Molecular Severo Ochoa Immunotech, Marseille, France Ortho Diagnostic B. CHU de Purpan Becton Dickinson Becton Dickinson Becton Dickinson Becton Dickinson Becton Dickinson Caltag, Burlingame, CA a P, purified mAb; AF, ascitic fluid mAb; S, mAb supernatant; AS, antiserum. CD8ϩ and CD4ϩ T lymphocytes assemble or process TCR1⁄7CD3 complexes, which are revealed when CD3␥ is absent
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