COMPLETE NUCLEOTIDE-SEQUENCE OF A GENOMIC CLONE ENCODING HLA-B35 ISOLATED FROM A CAUCASIAN INDIVIDUAL OF HISPANIC ORIGIN - IDENTIFICATION OF A NEW VARIANT OF HLA-B35

The primary structure of an HLA class I genomic clone isolated from a homozygous HLA-B35 Caucasian individual of hispanic origin was determined. The nucleotide sequence of exons 1, 2, 4, 5, 6, and 7 is identical to that of the HLA-B35 allele of Oriental origin reported previously. Exon 3 differs in only three nucleotides present in a stretch of 23 bp. These changes introduce three amino acid substitutions in residues 109 (Leu --> Phe), 114 (Asp --> Asn), and 116 (Ser --> Tyr), two of which (114 and 116) are located in one of the beta-sheets at the bottom of the peptide binding site. The nature of these replacements in this HLA-B35 variant is likely to affect peptide binding and recognition by T lymphocytes. Introns 1, 2, 3, 4, 5, and 6 from this genomic clone are identical to those present in HLA-Bw58, further confirming the evolutionary origin of HLA-B35.