- Email: [email protected]
A novel HLA-A allele bearing the HLA-BW4 sequence motif
Abstracts
2.1 #3
POSSISLE LINKAGE OF THE HLA-S15 GROUP TO HLA-CW INCLUDING FOUR NEW HLA-C ALLELES. J Hopfield, Y Mitsuishi, P Ge, KI Sibee, MP Settinotti, M Lau and P I Terasaki, UCLA Tissue Typing Laboratory, Los Angeles, CA Recent developments in DNA typing and sequencing for HLA class 1 have revealed tremendous numbers of new alleles at each locus. This is especially true in HLA-S15; 31 different sequences for this group are listed by the WHO nomenclature committee. HLA-S46 can also be included in this group. The International Cell Exchange program has recently begun to compare serological and DNA Class I typing data. One of its focuses is on HLA-S15. Our group is submitting sequencing data of HLA-A,S and C to this program. It seems that most of the HLA-S15 alleles are racially localized and have a significant linkage with HLA-Cw: most S62 and S76 (S*1512/-14) are linked with HLA-Cw3, Japanese S*1501 with Cw4, S*1502/-13 with Cw8, S*1519/-21 with Cw6, S46, S*1508/-11/-15 with Cw1, S*1509/-13/-17/-18/-23 with Cw7, S*1503/-09 with Cw2, S*1516 from African American with Cw16. For the last 4 linkage groups, 4 new HLA-C sequences have been identified. The new Cw1 sequence, found in Chinese, differs from HLA-Cw*0102 in exon3 (69:G->A, 76:A->T), which results in 2 amino acid replacements. The difference between the new Cw7 and Cw*0704 occurs in exon3 (169: T->G) and results in a single residue replacement. The last 2 variants were found only in African Americans. One is a new Cw*0202 allele (exon 3; 143:A->G), which is a silent mutation. The other is the new Cw*16 in which 3 nucleotides differ from Cw*1601 in exon3, resulting in the replacement of 2 amino acid residues. Further knowledge of the linkage between H LA-S and -C may be helpful in understanding the evolution of H LA-S 15 and obtaining accurate typing for clinical use, especially for oriental and hispanic populations.
2.1 #4
A NOVEL HLA-A ALLELE BEARING THE HLA-BW4 SEQUENCE MOTIF. DA Youngs, M Pandapurkur, J Anderson, LK Gaur, Immunogenetics Laboratory, Puget Sound Blood Center, Seattle, WA. Our laboratory has previously described a novel HLA-A antigen (locally identified as A3.32) whose uniqueness was based on observations of serological reactions. The antigen was peculiar in that it reacted positively with sera defining HLA-A3, HLA-A32 and Bw4. Based on the reactions of antisera defining particular A3, A32 and Bw4 epitopes and the known amino acid sequences of A3 and A32, it was speculated that the alpha-l domain should be A32-like, while the alpha-2 domain should be A3-like. Nucleotide sequencing of the gene encoding A3.32 has now been completed. The second exon does indeed resemble the second exon sequence of A*3201, which would result in an A32like alpha-I domain. The third exon begins like A*3201 (including guanine at exon 3 position #20), but switches to an A*0301-like sequence by position # 42 (thymine instead of cytosine). The remainder of the third exon sequence for the A3.32 gene matches that of A*0301, resulting in an alpha-2 domain which is, except for one amino acid (M97), identical to that for A3. Certain A-locus alleles (A*2301, A*2401, A*2402, A*2403, A*2405, A*2406, A*2407, A *250 I, A *320 I) contain a sequence motif in the second exon shared by approximately 40% of HLA-B alleles. This motif encodes the Bw4 epitope. The A3.32 allele also bears the Bw4 sequence motif, and thus explains the reactivity of Bw4 antisera with cells bearing the A3.32 antigen. We have observed A3.32 (based on serological results) in six Caucasian individuals, all but two of which are unrelated. In the two related individuals, the A3.32 antigen was found on a B35-DRI haplotype. The other four individuals possessing A3.32 all type positively for B35, and for DRI (one individual not DR-typed). A3.32 appears to have been generated from a recombinational event between A *030 1 and A *3201 between positions 20 and 42 of the third exon, and involving the common Caucasian haplotype A3-B35-DRI.
2.1 #3
POSSISLE LINKAGE OF THE HLA-S15 GROUP TO HLA-CW INCLUDING FOUR NEW HLA-C ALLELES. J Hopfield, Y Mitsuishi, P Ge, KI Sibee, MP Settinotti, M Lau and P I Terasaki, UCLA Tissue Typing Laboratory, Los Angeles, CA Recent developments in DNA typing and sequencing for HLA class 1 have revealed tremendous numbers of new alleles at each locus. This is especially true in HLA-S15; 31 different sequences for this group are listed by the WHO nomenclature committee. HLA-S46 can also be included in this group. The International Cell Exchange program has recently begun to compare serological and DNA Class I typing data. One of its focuses is on HLA-S15. Our group is submitting sequencing data of HLA-A,S and C to this program. It seems that most of the HLA-S15 alleles are racially localized and have a significant linkage with HLA-Cw: most S62 and S76 (S*1512/-14) are linked with HLA-Cw3, Japanese S*1501 with Cw4, S*1502/-13 with Cw8, S*1519/-21 with Cw6, S46, S*1508/-11/-15 with Cw1, S*1509/-13/-17/-18/-23 with Cw7, S*1503/-09 with Cw2, S*1516 from African American with Cw16. For the last 4 linkage groups, 4 new HLA-C sequences have been identified. The new Cw1 sequence, found in Chinese, differs from HLA-Cw*0102 in exon3 (69:G->A, 76:A->T), which results in 2 amino acid replacements. The difference between the new Cw7 and Cw*0704 occurs in exon3 (169: T->G) and results in a single residue replacement. The last 2 variants were found only in African Americans. One is a new Cw*0202 allele (exon 3; 143:A->G), which is a silent mutation. The other is the new Cw*16 in which 3 nucleotides differ from Cw*1601 in exon3, resulting in the replacement of 2 amino acid residues. Further knowledge of the linkage between H LA-S and -C may be helpful in understanding the evolution of H LA-S 15 and obtaining accurate typing for clinical use, especially for oriental and hispanic populations.
2.1 #4
A NOVEL HLA-A ALLELE BEARING THE HLA-BW4 SEQUENCE MOTIF. DA Youngs, M Pandapurkur, J Anderson, LK Gaur, Immunogenetics Laboratory, Puget Sound Blood Center, Seattle, WA. Our laboratory has previously described a novel HLA-A antigen (locally identified as A3.32) whose uniqueness was based on observations of serological reactions. The antigen was peculiar in that it reacted positively with sera defining HLA-A3, HLA-A32 and Bw4. Based on the reactions of antisera defining particular A3, A32 and Bw4 epitopes and the known amino acid sequences of A3 and A32, it was speculated that the alpha-l domain should be A32-like, while the alpha-2 domain should be A3-like. Nucleotide sequencing of the gene encoding A3.32 has now been completed. The second exon does indeed resemble the second exon sequence of A*3201, which would result in an A32like alpha-I domain. The third exon begins like A*3201 (including guanine at exon 3 position #20), but switches to an A*0301-like sequence by position # 42 (thymine instead of cytosine). The remainder of the third exon sequence for the A3.32 gene matches that of A*0301, resulting in an alpha-2 domain which is, except for one amino acid (M97), identical to that for A3. Certain A-locus alleles (A*2301, A*2401, A*2402, A*2403, A*2405, A*2406, A*2407, A *250 I, A *320 I) contain a sequence motif in the second exon shared by approximately 40% of HLA-B alleles. This motif encodes the Bw4 epitope. The A3.32 allele also bears the Bw4 sequence motif, and thus explains the reactivity of Bw4 antisera with cells bearing the A3.32 antigen. We have observed A3.32 (based on serological results) in six Caucasian individuals, all but two of which are unrelated. In the two related individuals, the A3.32 antigen was found on a B35-DRI haplotype. The other four individuals possessing A3.32 all type positively for B35, and for DRI (one individual not DR-typed). A3.32 appears to have been generated from a recombinational event between A *030 1 and A *3201 between positions 20 and 42 of the third exon, and involving the common Caucasian haplotype A3-B35-DRI.