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2.2.2 MHC G-DOMAINs
The four G-DOMAINs, G-ALPHA1 and G-ALPHA2 of the MHC-I, and G-ALPHA
and G-BETA of the MHC-II (Figs. 1, 4, and 5), have a similar groove 3D structure
that consists of one sheet of four antiparallel β strands (“floor” of the groove or plat-
form) and one long helical region (“wall” of the groove) (Lefranc et al. 2005b). For
each G-DOMAIN (Figs. 4 and 5), the A strand comprises positions 1 to 14, B strand
positions 18 to 28, C strand positions 31 to 38, and D strand positions 42 to 49
(Lefranc et al. 2005b). The helix (positions 50 to 92) seats on the β sheet and its axis
forms an angle of about 40 degrees with the β strands. The helix is split into two
parts separated by a kink, positions 58 of G-ALPHA1, 61 of G-ALPHA2, 63 of G-
ALPHA, and 62 of G-BETA being the “highest” points on the floor groove. The G-
ALPHA2 and G-BETA domains have a disulfide bridge between positions 11 and
74. The G-ALPHA1 and G-ALPHA domains have a conserved N-glycosylation site
at position 86 (N-X-S/T, where N is asparagine, X any amino acid except proline, S
is serine, and T is threonine), except for HLA-DMB and H2-DMB1. Asparagine 15
of the G-BETA domains also belongs to a conserved N-glycosylation site (Lefranc
et al. 2005b).
2.3 TR/pMHC Contact Analysis
2.3.1 Peptide/MHC
The 3D structure of the MHC main chain is well conserved and the peptide bind-
ing groove specificity is due to side chain physicochemical characteristics (Reinherz
et al. 1999). Both MHC-I and MHC-II grooves have pockets where side chains
of bound peptides may anchor (Falk, Rotzschke, Stevanovic, Jung, and Rammen-
see 1991), the specificity of a peptide to a given MHC being controlled by the
physicochemical properties of the pockets. Conversely, comparisons of peptide
sequence alignments and pMHC 3D structures have revealed that some anchored
peptide positions with conserved properties were needed to bind a peculiar MHC
allele. Several databases, SYFPEITHI (Rammensee, Bachmann, Emmerich,
Bachor, and Stevanovie 1999), JenPep (Blythe, Doytchinova, and Flower 2002),
and MHCpep (Brusic, Rudy, and Harrison 1998), provide peptide sequences
associated with MHC alleles together with anchor positions and experimental
data on affinity. These observations have extensively been used in peptide/MHC
binding prediction (Singh and Raghava 2003; Adams and Koziol 1995; Vasmat-
zis, Zhang, Cornette, and DeLisi 1996b). A list of prediction programs and serv-
ers is available at “The IMGT Immunoinformatics page” (http://imgt.cines.fr).
Nevertheless, exceptions have been found (Mandelboim, Bar-Haim, Vadai, Frid-
kin, and Eisenbach 1997; Apostolopoulos, Yu, Corper, Teyton, Pieters,
McKenzie, and Wilson 2002; Scott, Peterson, Teyton, and Wilson 1998) and it
was noted that while only 30% of peptides with the expected pattern really bind,
peptides without the expected pattern also bind (Gulukota, Sidney, Sette, and
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