The influence of varying degrees of incompatibility for HL-A antigens on one-way mixed lymphocyte cultures (MLC) has been investigated. Reactions have been compared to a simple expression of HL-A antigens, allele compatibility, and a proposal considering the potential influence of antigen matching in relationship to allele compatibility.

As expected, HL-A compatibility was associated with nonstimulated cultures, but significant correlation was not observed when incompatibility was expressed in terms of HL-A antigen or allele mismatching.

When the relationship of both was considered, however, a second distinctive group was demonstrated that shared one allele plus one antigen of the second allele. Within this group no stimulation, even with augmented culture conditions, was observed in some families. Employing these same criteria, there was no significant difference in the MLC response in those groups that were incompatible for both alleles regardless of the number of matched antigens or the group that shared an allele but differed by both antigens of the second allele.

These results support the concept of an intimate relationship between the loci coding for HL-A antigens and mixed culture reactions. They suggest that HL-A haplotype incompatibility acting as a unit is the primary stimulus of the MLC response, and that the immunogenicity of the haplotype also relates to whether or not one antigen is common to the stimulating and responding cell.

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