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Full-length cDNA sequencing of the A*1103 allele revealed an insertion of 18 bp between exon 5 and 6. We hypothesized that this could be the result of alternative splicing. Sequencing of intron-5 of A*1101, *1102 and *1103 alleles demonstrated that this 18-bp insertion consisted of the 5'-end of intron 5, concluded by a second in-frame donor splice site. Alignment of the 5'-end intron 5 sequence of A*1101-3 with that of A*0101, *0201 and 0301 revealed a unique polymorphism at position 17 of the intron (A to G) that created this second donor splice site. To exclude the possibility of an Epstein-Barr virus (EBV)-induced event, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed on both peripheral blood mononuclear cells (PBMC) and EBV-transformed b-LcL's of several A*11-positive individuals, using primers spanning exons 5 and 6. Without exception, both cell types revealed two products for A*11. Densitometric analysis using EBV-transformed b-LcL's and PBMC indicated a ratio of approximately 4:1 in favor of the alternative splice product. Notably, except for the A*11's none of the other A-locus alleles yields this alternative splice product. Translation of this product will result in a protein that has an additional 6 amino acids in its cytoplasmic domain. This introduces a negative charge just behind the basic anchor residues of the cytoplasmic segment and results in the loss of the single potential protein kinase C phosphorylation site.

Recent genome-wide association studies have identified several genetic risk factors for psoriasis, but data on their association with age at onset are lacking.To compare the association between known risk alleles and psoriasis in well-defined cohorts with paediatric- and adult-onset psoriasis.Based on previous studies we selected seven genes and loci associated with psoriasis. Patients with paediatric-onset (18 years) and adult-onset psoriasis (≥ 18 years) and controls were genotyped. Genotype frequencies were compared between controls (n = 450) and all cases (n = 217), and between controls and cases stratified for confirmed age at onset (paediatric onset n = 80, adult onset n = 85).Paediatric-onset psoriasis showed a significant association with single nucleotide polymorphisms in the ERAP1 (P = 0.042) and IL23R loci (P = 0.042), LCE3C_LCE3B-del (P = 0.003) and HLA-C*06 (P = 1.72 × 10(-19)) when compared with the control group. A significant association of these four genes was also demonstrated when all psoriasis cases were compared with controls. In adult-onset psoriasis a significant association was found for HLA-C*06 (P = 5.11 × 10(-6)) and for LCE3C_LCE3B-del (P = 0.042). No associations were found for the IFIH1, IL12B and TRAF3IP2 loci.Notwithstanding the small cohort sizes, we demonstrated an association with established and recently discovered genetic risk factors in paediatric-onset psoriasis including genes involved in epidermal barrier function and adaptive immunity. Our data suggest that heritable factors may play a more important role in paediatric-onset psoriasis than in adult-onset psoriasis.

Here we report the full-length sequence of a novel A*11 variant. The variant was identified by ARMS-PCR and serology, the sequence was confirmed by cloning and subsequent sequencing. This variant, A*1103, found in a family of oriental origin, resembles the A*1101 sequence in exon 2 but differs in exon 3 with regard to codons 151 and 152. The polymorphism’s result in two amino acid substitutions (one conserved (His->Arg), one introducing a negative charge (Ala->Glu)) located in the α2 helical region. The arginine at amino acid position 151 is rare amongst A-locus alleles and is besides A*1103 only observed in A*29 variants, the glutamine at amino acid position 152 is shared with A*0301, A*25, *26, *34 variants and the A*02 subtypes A*0203, *0213 and *0226. In fact, the amino acid motif comprising codons 151 and 152 is unique to A*1103 among A-locus alleles, but is common to C-locus alleles ( Note).

Biochemical and serological methods were used to characterize sheep MHC class I polymorphism at the product level. The cells of 65 selected animals were subjected to immunoprecipitation and one-dimensional isoelectric focusing (IEF) with two cross-reacting monoclonal antibodies, B1.1G6 and HC-10. We were able to define up to 18 distinct haplotypes in the Latxa breed sample. Most of the locally defined serological specificities were confirmed or subdivided by biochemical typing. As IEF detected antigens not yet defined by serology, it provided us with a guide to producing more specific antisera by appropriate immunizations. Lastly, evidence of expression of two class I loci products was found.

We describe the identification of a new DRB1*03 variant in a Caucasian volunteer bone-marrow donor (DR'KW'). The indication for the existence of this new variant arose from contradictory results obtained by serological and several DNA typing methods (SSP, SSOP). Analysis of the exon 2 sequence revealed that the DRB1*0314 contained the characteristic DR3 specific sequence motifs, except for codon 77 (AAC--ACC) where threonine is substituted for asparagine.