HIGH-RESOLUTION HLA-C TYPING BY PCR-SSP - IDENTIFICATION OF ALLELIC FREQUENCES AND LINKAGE DISEQUILIBRIA IN 604 UNRELATED RANDOM UK CAUCASOIDS AND A COMPARISON WITH SEROLOGY (VOL 48, PG 680, 1996)

Recent evidence indicates that HLA-C molecules are biologically releva nt by eliciting T-cell responses and exerting control over NK cell fun ction. In addition, HLA-C is associated with susceptibility to various diseases, notably psoriasis vulgaris. Clarification of the full biolo gical roles for HLA-C has however proved difficult because detection o f HLA-C antigens by complement mediated cytotoxicity using alloantiser a is inefficient. Up to 50% of individuals in every race have serologi cally undetectable HLA-C locus antigens due to a combination of relati vely low expression, lack of serological reagents and a lack of inform ation about the distribution of the HLA-C blank alleles. Recently, amp lification of DNA using sequence-specific primers (PCR-SSP) has proved a reliable, accurate and rapid method for medium resolution HLA-C typ ing. We have now developed high resolution HLA-C typing by PCR-SSP uti lizing allele and group-specific PCR-SSP reactions which can identify all HLA-C alleles (except non-coding change alleles) in most heterozyg ous combinations. Using this system we have typed 604 unrelated United Kingdom Caucasoids to generate accurate frequency and linkage disequi librium data. To assess the validity of serology for HLA-C, PCR-SSP ty pings for 527 out of the 604 individuals were compared to serology. We find that the frequency of many HLA-C antigens has been underestimate d by serology and some antigens such as Cw6 are consistently assigned incorrectly by serology. The overall discrepancy rate between serology and SSP was high at 37% (195/527). High-resolution HLA-C typing of 11 2 International Histocompatibility Workshop cell lines has also been p erformed.