T8 and T3 surface glycoproteins in human T-cell mediation of leukocyte adherence inhibition to extracts of autologous cancer.
Monoclonal antibodies (MAb's) [anti-Leu-1, anti-Leu-2a (T8), anti-Leu-3a (T4), and anti-Leu-4 (T3)] were used to elucidate the type of T-cell mediating leukocyte adherence inhibition (LAI) and the role of T-cell surface glycoproteins in LAI. T8+ (Leu-2a+) and T4+ (Leu-3a+) subtypes were isolated by panning. T8+ (Leu-2a+) cells showed LAI to extracts of autologous cancer, whereas the T4+ (Leu-3a+) subset had no LAI response. Moreover, MAb to the T8+ (Leu-2a+) glycoprotein negated T-cell LAI, but MAb to Leu-1+ or to T4+ (Leu-3a+) did not negate T-cell LAI to autologous cancer extracts. The T3+ (Leu-4+) differentiation also was essential for T-cell LAI to autologous cancer extracts since anti-Leu-4 (T3) negated the response. Since LAI to autologous cancer extracts depends ultimately on leukotriene and other oxidative metabolites of arachidonic acid generated by the T-cell binding tumor antigen, the effect of MAb on LAI induced by leukotriene B4 isomer III. 5(S), 12(R)-dihydroxy-6, 14-cis-8, 10-trans-eicosatetraenoic acid (LTB4) was examined. Authentic LTB4 induced nonadherence of 34% of adherent T-cells, and this effect was not negated by anti-Leu-1, anti-T8 (Leu-2a), or anti-T4 (Leu-3a). However, anti-T3 (Leu-4) abrogated LTB4-induced LAI of pure T-cells without any effect on the basic adherence properties of T-cells. The present findings indicated that LAI to autologous cancer extracts was mediated by T-cells of the T8+ phenotype when they recognize tumor antigen and polymorphic major histocompatibility complex determinants on autologous cancer membranes. Moreover, differentiation glycoproteins T8+ (Leu-2a+) and T3+ (Leu-4+) on the surface of the responding effector T-cells performed distinct biologic functions that enabled the tumor antigen to trigger T-cell LAI.
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology / Q000502:physiology*; D001943:Breast Neoplasms / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007957:Leukocyte Adherence Inhibition Test; D007975:Leukotriene B4 / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D006023:Glycoproteins; D008565:Membrane Proteins; D007975:Leukotriene B4