Differential antibody binding to the surface alphabetaTCR.CD3 complex of CD4+ and CD8+ T lymphocytes is conserved in mammals and associated with differential glycosylation.
We have previously shown that the surface alphabeta T cell antigen receptor (TCR).CD3 complex borne by human CD4(+) and CD8(+) T lymphocytes can be distinguished using mAbs. Using two unrelated sets of antibodies, we have now extended this finding to the surface alphabetaTCR.CD3 of seven additional mammalian species (six non-human primates and the mouse). We have also produced data supporting that differential glycosylation of the two main T cell subsets is involved in the observed TCR.CD3 antibody-binding differences in humans. First, we show differential lectin binding to human CD4(+) versus CD8(+) T lymphocytes, particularly with galectin 7. Second, we show that certain lectins can compete differentially with CD3 mAb binding to human primary CD4(+) and CD8(+) T lymphocytes. Third, N-glycan disruption using swainsonine was shown to increase mAb binding to the alphabetaTCR.CD3. We conclude that the differential antibody binding to the surface alphabetaTCR.CD3 complex of primary CD4(+) and CD8(+) T lymphocytes is phylogenetically conserved and associated with differential glycosylation. The differences may be exploited for therapeutic purposes, such as T cell lineage-specific immunosuppression of graft rejection. Also, the impact of glycosylation on CD3 antibody binding requires a cautious interpretation of CD3 expression levels and T cell numbers in clinical diagnosis.
Rossi
Nineth E
NE
Inmunología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Reiné
Jesús
J
Pineda-Lezamit
Miguel
M
Pulgar
Manuel
M
Meza
Néstor W
NW
Swamy
Mahima
M
Risueno
Ruth
R
Schamel
Wolfgang W A
WW
Bonay
Pedro
P
Fernández-Malavé
Edgar
E
Regueiro
José R
JR
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000915:Antibody Affinity / Q000276:immunology; D015704:CD4 Antigens; D016827:CD8 Antigens; D019143:Evolution, Molecular; D006031:Glycosylation; D006801:Humans; D007165:Immunosuppression Therapy; D019169:Jurkat Cells; D037102:Lectins / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011323:Primates; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D012680:Sensitivity and Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D037102:Lectins; D008562:Membrane Glycoproteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell