A TYPING SYSTEM FOR THE EXTERNAL DOMAIN ALLELES OF MICA.
RW Vaughan, HAF Stephens*, J Theron, E Kondeatis. Tissue Typing,
Guy's Hospital & UCH*, London, UK.
MICA is a highly polymorphic series of HLA Class I related
genes coded for at a locus close to and centromeric of HLA-B. Current evidence
indicates that MICA genes are normally expressed on gut epithelial cells,
endothelial and keratinocyte cells and that they may be capable of antigen
presentation. We have taken the sixteen published nucleotide sequences
(1) and designed a PCR/SSP (aka ARMS) system to attempt specific detection
of the known alleles. Using twelve cell lines that are known to have eleven
of the sequenced alleles (1) we have obtained amplification products of
the correct predicted size. We have incorporated some broadly specific
reactions in order to detect unknown alleles, and the current typing system
consists of twenty-four reactions. We have used this typing system on a
three generation family and shown that MICA amplification products segregate
with the MHC haplotypes. In 50 cell lines selected for polymorphism at
HLA-B we have obtained reaction patterns consistent with known alleles,
but as indicated from the amplification patterns, there appear to be alleles
whose sequence is not yet described. In normal controls it is possible
to distinguish heterozygous combinations of alleles, and again there is
evidence for new alleles. In conclusion we present a simple MICA typing
scheme which is able to identify most of the currently recognised alleles
unequivocally and is useful in indicating possible new alleles. The system
is being used to examine various ethnic groups and disease cohorts. We
plan to extend our typing system as we sequence new alleles, and as further
alleles are published. (1) Fodil et al Immunogenetics 1996, 44,351-7