Major histocompatibility complex recognition by immune receptors: differences among T cell receptor versus antibody interactions with the VSV8/H-2Kb complex.
The surface residues of the VSV8/Kb complex important for recognition by N15 and N26 alphabeta T cell receptors (TCR) were mapped by mutational analysis and compared to each other and with epitopes of well-characterized Kb specific monoclonal antibodies (mAb). Three features of immune receptor recognition emerge. First, the footprints of the two TCR on VSV8/Kb are similar with more than 80 % overlap between sites. Given that only 8 of 14 surface exposed VSV8/Kb residues identified as critical for TCR interaction are in common, the chemical basis of the N15 and N26 interactions is nevertheless distinct. Second, the cognate peptide is a major focus of TCR recognition: mutation at any of the three exposed side chains (at p1, p4 or p6) abrogates interaction of both TCR as measured by functional T cell activation. Third, in contrast to TCR, mAb bind to discrete segments on the periphery of the alpha1 and/or alpha2 helices without orientational restriction. These findings suggest that unlike soluble antibodies, surface membrane receptor-ligand interactions on opposing cells (i.e. TCR-peptide/ MHC, CD8-MHC) limit the orientational freedom of the TCR in the immune recognition process.
Witte
T
T
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Smolyar
A
A
Spoerl
R
R
Goyarts
E C
EC
Nathenson
S G
SG
Reinherz
E L
EL
Chang
H C
HC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D018604:Epitope Mapping; D006183:H-2 Antigens / Q000502:physiology*; D051379:Mice; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000276:immunology; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D006183:H-2 Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell