A role for the region encompassing the c '' strand of a TCR V alpha domainin T cell activation events

The distinct strand topology of TCR V alpha domains results in a flatter su rface in the region encompassing the c " strand than the corresponding regi on in Ig V domains. In the current study a possible role for this region in T cell activation has been investigated by inserting a potential glycosyla tion site at V alpha residue 82, This residue is in proximity to the c " st rand and distal to the putative interaction site for cognate peptide:MHC li gand, An additional N-linked carbohydrate at this position would create a p rotrusion on the V alpha domain surface, and this may interfere with TCR ag gregation and/or recruitment of signaling molecules. The modified TCR has b een expressed in transfected T cells, and the phenotype following stimulati on has been compared with that of cells expressing the wild-type TCR, The m utation has significant effects on activation-induced cell death and TCR in ternalization, but, unexpectedly, does not affect IL-2 secretion, Furthermo re, analyses with tetrameric, peptide:MHC class II complexes suggest that t he mutation decreases the ability of the TCR to aggregate into a configurat ion compatible with avid binding by these multivalent ligands.