A new classification of HLA-DRB1 alleles differentiates predisposing and protective alleles for autoantibody production in rheumatoid arthritis

Table 1 HLA–DRB1 amino acid sequence for alleles observed among rheumatoid arthritis patients and their classification according to du Montcel and colleagues

HLA-DRB1 allele	Amino acid position								Classification of du Montcel and colleagues
	69	70	71	72	73	74	75	76
HLA-DRB1*0101	E	Q	R	R	A	A	V	D	S3P
HLA-DRB1*0102	-	Q	R	R	A	A	-	-	S3P
HLA-DRB1*0103	-	D	E	R	A	A	-	-	S1
HLA-DRB1*03	-	-	K	-	G	R	-	-	X
HLA-DRB1*0401	-	Q	K	R	A	A	-	-	S2
HLA-DRB1*0402	-	D	E	R	A	A	-	-	S1
HLA-DRB1*0403	-	-	-	-	-	E	-	-	X
HLA-DRB1*0404	-	Q	R	R	A	A	-	-	S3P
HLA-DRB1*0405	-	Q	R	R	A	A	-	-	S3P
HLA-DRB1*0407	-	-	-	-	-	E	-	-	X
HLA-DRB1*0408	-	Q	R	R	A	A	-	-	S3P
HLA-DRB1*0411	-	-	-	-	-	E	-	-	X
HLA-DRB1*07	-	D	-	-	G	Q	-	-	X
HLA-DRB1*08	-	D	-	-	-	L	-	-	X
HLA-DRB1*0901	-	R	-	-	-	E	-	-	X
HLA-DRB1*1001	-	Q	R	R	A	A	-	-	S3P
HLA-DRB1*1101	-	D	R	R	A	A	-	-	S3D
HLA-DRB1*1102	-	D	E	R	A	A	-	-	S1
HLA-DRB1*1103	-	D	E	R	A	A	-	-	S1
HLA-DRB1*1104	-	D	R	R	A	A	-	-	S3D
HLA-DRB1*12	-	D	R	R	A	A	-	-	S3D
HLA-DRB1*1301	-	D	E	R	A	A	-	-	S1
HLA-DRB1*1302	-	D	E	R	A	A	-	-	S1
HLA-DRB1*1303	-	D	K	R	A	A	-	-	S2
HLA-DRB1*1323	-	D	E	R	A	A	-	-	S1
HLA-DRB1*1401	-	R	-	-	-	E	-	-	X
HLA-DRB1*1402	-	Q	R	R	A	A	-	-	S3P
HLA-DRB1*1404	-	R	-	-	-	E	-	-	X
HLA-DRB1*15	-	Q	A	R	A	A	-	-	S1
HLA-DRB1*16	-	D	R	R	A	A	-	-	S3D

In the du Montcel and colleagues classification [35], the HLA–DRB1 alleles were first divided into two groups according to the presence or absence of the RAA sequence at positions 72–74, which denote S and X alleles (respectively shared epitope and nonshared epitope alleles). The S alleles were subsequently divided into four groups according to the two first amino acids at positions 70 and 71 (boldface): S1 for ARAA and ERAA, S2 for KRAA, S3 for RRAA (divided into S3P for QRRAA and S3D for DRRAA according to position 70), and X for all non-RAA motifs. The conventional classification of the amino acids was used, here divided into three biochemical subgroups, as follows: group 1 = G for glycine, A for alanine, V for valine, L for leucine (aliphatic amino acids (nonpolar hydrophobic)); group 2 = K for lysine, R for arginine (basic amino acids (polar and positively charged)); group 3 = E for glutamic acid, Q for glutamine (the amide corresponding to E), D for aspartic acid, and N for asparagine (the amide corresponding to D) (acidic amino acids and corresponding amides are very hydrophilic; acidic amino acids are polar and negatively charged at physiologic pH, amides are polar and uncharged, and not ionizable) [36].

ISSN: 1478-6362