Differential antibody binding to the surface αβTCR·CD3 complex of CD4⁺ and CD8⁺ T lymphocytes is conserved in mammals and associated with differential glycosylation

TY - JOUR

T1 - Differential antibody binding to the surface αβTCR·CD3 complex of CD4+ and CD8+ T lymphocytes is conserved in mammals and associated with differential glycosylation

AU - Rossi, Nineth E.

AU - Reiné, Jesús

AU - Pineda-Lezamit, Miguel

AU - Pulgar, Manuel

AU - Meza, Néstor W.

AU - Swamy, Mahima

AU - Risueno, Ruth

AU - Schamel, Wolfgang W.A.

AU - Bonay, Pedro

AU - Fernández-Malavé, Edgar

AU - Regueiro, José R.

PY - 2008/10/6

Y1 - 2008/10/6

N2 - We have previously shown that the surface αβ 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 αβTCR·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 αβTCR·CD3. We conclude that the differential antibody binding to the surface αβTCR·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.

AB - We have previously shown that the surface αβ 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 αβTCR·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 αβTCR·CD3. We conclude that the differential antibody binding to the surface αβTCR·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.

KW - Cell surface molecules

KW - T cells

KW - TCRs

UR - https://www.scopus.com/pages/publications/52949140870

U2 - 10.1093/intimm/dxn081

DO - 10.1093/intimm/dxn081

M3 - Article

C2 - 18653700

AN - SCOPUS:52949140870

SN - 0953-8178

VL - 20

SP - 1247

EP - 1258

JO - International Immunology

JF - International Immunology

IS - 10

ER -