HLA-DQA1 and MLC among HLA (generic)-identical unrelated individuals

We modified a previously published PCR-RFLP for DQA1 typing (1) and examined the predictive value of HLA-DQA1 in mixed lymphocyte cultures (MLC) among matched (HLA generic types) pairs of unrelated individuals. There were 61/102 (60%) pairs with positive MLC, one-third of which could be predicted by DQA1* typing alone. DQA1 matching and MLC reactions were classified into 3 groups: 1) DQA1 mismatches showing positive MLC: 19/102 (19%); 2) DQA1 matches showing negative MLC: 41/102 (40%); 3) DQA1 identical showing positive MLC: 42/102 (41%). Five different HLA haplotypes that result from non-random association of HLA generic types (high delta haplotypes) were overrepresented in the individuals tested. One of these haplotypes carrying HLA-B7, DR2 was found associated with three different DQA1 alleles (*0201, *0103, *0102). The remaining four high delta haplotypes were associated with one DQA1 allele in all independent examples tested: HLA-A1, B8, DR3 with DQA1*0501; HLA-A26, B38, DR4 with DQA1*0301; HLA-A2, Bw62, DR4 with DQA1*0301 and HLA-A1, Bw57, DR7 with DQA1*0201. Forty per cent of the negative MLC were explained in part by the excessive number of individuals carrying two of these four haplotypes, which probably carry determinants in linkage disequilibrium with HLA. Nineteen per cent of HLA-identical (generic types) unrelated pairs show positive MLC reactions and all of them are DQA1* mismatched, suggesting that DQA1* allele typing should be used to screen samples prior to performing MLC.