HLA class II molecules transduce accessory signals affecting the CD3 but not the interleukin-2 activation pathway in T blasts.
MHC class II molecules play a central role in the control of the immune response, but their biologic function and mechanism of action on the surface of activated human T lymphocytes are not entirely understood. In our study, the functional role of HLA class II molecules in T-blast proliferation was investigated by analyzing in parallel the IL-2- and CD3-driven activation pathways. The results indicate that the cross-linking of class II and CD3 molecules significantly increased the CD3-mediated T-blast proliferation, while no effect was observed on the IL-2-driven cell activation. This phenomenon was not confined to either CD4+ or CD8+ subsets nor was specifically affected by CD45 triggering. Biochemical studies showed that signaling via MHC class II molecules in T blasts led to PKC membrane translocation and IP accumulation. The simultaneous triggering of CD3 and HLA class II molecules led to a synergistic effect on IP accumulation but did not increase the CD3-mediated PKC membrane translocation. Our data suggest that HLA class II molecules are involved in T-cell-T-cell interactions and can mediate accessory signals, affecting the T-lymphocyte activation state.
Di Rosa
F
F
Department of Cellular and Molecular Biology and Pathology, Federico II University of Naples, Italy.
D'Oro
U
U
Ruggiero
G
G
Racioppi
L
L
Acquaviva
A
A
Ferrone
S
S
Fontana
S
S
Zappacosta
S
S
D017252:CD3 Complex / Q000502:physiology*; D006681:HLA-D Antigens / Q000502:physiology*; D006801:Humans; D007295:Inositol Phosphates / Q000097:blood; D007376:Interleukin-2 / Q000502:physiology*; D008213:Lymphocyte Activation; D011493:Protein Kinase C / Q000097:blood; D015398:Signal Transduction / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D017252:CD3 Complex; D006681:HLA-D Antigens; D007295:Inositol Phosphates; D007376:Interleukin-2; D011493:Protein Kinase C