The Co-operative Specificity Theory: phenotypic protection from T1D by certain HLA Class II DRB1 and DQ alleles identifies the absence of co-operation between the respective DR and DQ molecules eventuating in no T1D-predisposition.

It is well established that both DR and DQ genes are involved in type 1 diabetes (T1D) -susceptibility. But how the DR and DQ molecules contrive to effect collectively the same function of T1D predisposition remains unexplained. We advance the Co-operative Specificity Theory which attempts to project the relationship by which this occurs. The Co-operative Specificity Theory says that what is involved and being observed is a phenomenon of specific reciprocal recognition between corresponding DR- and DQ-molecules in a haplotype, resulting in a co-operation that realizes effects: this specificity varies in degrees. It is a situation of co-operative participation restricted to a specific DR- and its corresponding specific DQ-molecules that results in susceptibility. Thus susceptibility may not result when a corresponding specific DR or DQ allele is substituted by a non-specific allele in the haplotype. It thus ensues that phenotypic protection identifies the absence of this specific co-operation between the respective DR and DQ molecules giving rise to no predisposition.