A new model defines the minimal set of polymorphism in HLA-DQ and -DR that determines susceptibility and resistance to autoimmune diabetes

Parry, Christian S; Brooks, Bernard R

doi:10.1186/1745-6150-3-42

Table 3 Selected alleles, their representative peptides and motifs

From: A new model defines the minimal set of polymorphism in HLA-DQ and -DR that determines susceptibility and resistance to autoimmune diabetes

Peptide	Sequence and motif	allele
	1xx4x6xx9
CLIP peptide 81–104	LPKPPKPVSK M RM A T P LL M QALPM	DR3
MET proto-oncogene 724–735	LKIDLANRETSI	DR3
HSP70 M leprae 261–280	DSDKNPLFLDEQLIRAEFQR	DR3
HSP70 M leprae 408–427	QPSVQIQVYQGEREIASHNK	DR3
SSX2 37–51	WEKMKASEKIFYVYM	DR3
Tetanus toxin 830–843	QY I KA N S K FI G ITE	DR3
Preproinsulin 78–88	QPLALEGSLQK	DR4
ER-60 protease	TEDEFKKFISDKDASVVG	DR4
14-3-3 epsilon 57–71	RASWRIISSIEQKEE	DR4
GAD65 274–286	IAFTSEHSHFSLK	DR4
GAD65 471–490	VDKCLELAEYLYNIIKNREG	DR4
Aminopeptidase 462–475	FELFPSLSHNLLVD	DR4
β2 microglobulin 64–78	LYYTEFTPTEKDEY	DR0405
der pII 58–73	IDGLEVDVPGIDPNA	DR0405
HSP90 beta 68–81	KELKIDIIPNPQER	DR0405
Fel d1 22–37	EQVAQYKALPVVLENA	DR0405
Integrin β3 24–39	AWCSDEALPLGSPRCD	DR52a
AChR alpha 144–163	MKLGTWTYDGSVVAINPESD	DR52a
AChR epsilon 201–219	ENGEWAIDFCPGVIRRHHG	DR52a
Lol p1 101–120	APYHFDLSGHAFGSMAKKG	DR52a
Influenza A HA 306–324	PKYVKQNTLKLATGMRNVP	DR7
HSP70 M Leprae 241–260	AKIELSSSQSTSVNLPYITV	DR7
HIV-1 RT 326–345	FRKQNPDIVIQYMDDLYVG	DR7
HLA class I α52–60	IEQEGPEYW	DQ2
Flu NP 265–278	IASNENMDAMESSTL	DQ2
M leprae 18 kD 31–43	DAWREGEEFVVEF	DQ2
Rabies virus NP 11–24	NNQVVSLKPEIIVDQ	DQ2
Thyroid peroxidase 632–645	IDVWLGGLAENFLP	DQ2
Thyroid peroxidase 632–645	IDVWLGGLAENFLP	DQ8
Trail receptor 2 364–380	GRFTYQNAAAQPETG	DQ8
Cyclophilin R 325–340	VDQWSTETIASHEDIE	DQ8
Cathepsin D 65–77	EPVSELLKNYLDA	DQ8
E25B protein 112–126	YQTIEENIKIFEEDA	DQ8
I-A2B 644–658	GGDPGADATAAYQEL	DQ8
I-A2B 762–776	KNRSLAVLTYDHSRV	DQ8
GAD65 121–140	YVVKSFDRSTKVIDFHYPNE	DQ8
GAD65 231–250	PGGSGDGIFSPGGAISNMYA	DQ8
GAD65 248–259	NYAMMIARFKMF	DR3
GAD65 250–273	AMMIARFKMFPEVKEKGMAALPRL	DQ8
GAD65 471–490	VDKCLELAEYLYNIIKNREG	DR4
I-A2 961–979	FEFALTAVAEEVNAIL	DQ8
I-A2 961–979	FEFALTAVAEEVNAIL	DQ8
ICA69 33–50	TKQAFIKATGKKEDEHVV	DQ8
Insulin B:9–23	SHLVEALYLVCGERG	DQ8
Insulin B:24-C:4	FFYTPKTRREAED	DQ8

Epitopes of several class II MHC molecules are aligned manually according to their pocket motif. The major diabetes susceptibility molecules DR3, DR4. DR405 and DQ8 show a strong preference for polar residues at position P9. Acidic residues such as Asp and Glu are common at this position but there are also basic and other polar residues. In contrast alleles that are neutral (DR7 and DR52a) show a preference for aliphatic and hydrophobic residues at P9. DQ2 shows no preference for acidic residues at P9 that characterize diabetogenic molecules. Sequence information comes from several sources including [46].

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ISSN: 1745-6150

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