NUCLEOTIDE-SEQUENCE ANALYSIS OF HLA-B-ASTERISK-1523 AND B-ASTERISK-8101 - DOMINANT ALPHA-HELICAL MOTIFS PRODUCE COMPLEX SEROLOGIC RECOGNITION PATTERNS FOR THE HLA-B''DT'' AND HLA-B''NM5'' ANTIGENS

Assigning a precise serologic specificity to the class I HLA-B''NM5'' and HLA-B''DT'' molecules has proven difficult, with patterns of serol ogic cross-reactivity suggesting that NM5 is most like antigens in the B5 CREG and that DT is either B7 or B40 like. To better understand th e relationship these antigens share with other HLA-B molecules we dete rmined the nucleotide sequence of the alleles encoding HLA-B''NM5'' an d HLA-B''DT''. Sequencing results show that NM5 shares the most overal l sequence homology with the B70 antigens and that differences at the alpha-helical Bw4/Bw6 epitope preclude serologic cross-reactivity betw een NM5 and the B70 antigens. Accordingly, NM5 has been assigned the n ame B1523. The strong serologic impact of helical sequence conservati ons and variations is reiterated for the class I HLA-B''DT'' molecule. Comparative analysis demonstrates that sequence conservations in the first domain's alpha-helix stimulate cross-reactivity between HLA-B''D T'' and HLA-B7, whereas epitopes conserved in the second domain's alph a-helix impel cross-reactivity between HLA-B''DT'' and HLA-B48. To con vey the unique lineage of this hybrid B7/B48 molecule the name HLA-B8 101 has been assigned to HLA-B''DT''.