title: Differential antibody binding to the surface alphabetaTCR.CD3 complex of CD4+ and CD8+ T lymphocytes is conserved in mammals and associated with differential glycosylation.
abstract: 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.
authors.affiliation: Inmunología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
authors.forename: Nineth E
authors.initials: NE
authors.lastname: Rossi
authors.forename: Jesús
authors.initials: J
authors.lastname: Reiné
authors.forename: Miguel
authors.initials: M
authors.lastname: Pineda-Lezamit
authors.forename: Manuel
authors.initials: M
authors.lastname: Pulgar
authors.forename: Néstor W
authors.initials: NW
authors.lastname: Meza
authors.forename: Mahima
authors.initials: M
authors.lastname: Swamy
authors.forename: Ruth
authors.initials: R
authors.lastname: Risueno
authors.forename: Wolfgang W A
authors.initials: WW
authors.lastname: Schamel
authors.forename: Pedro
authors.initials: P
authors.lastname: Bonay
authors.forename: Edgar
authors.initials: E
authors.lastname: Fernández-Malavé
authors.forename: José R
authors.initials: JR
authors.lastname: Regueiro
mesh_terms: 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*
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D037102:Lectins; D008562:Membrane Glycoproteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell