SELECTIVE EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) ANTIGENS AND MODULATION OF T-CELL DIFFERENTIATION IN CHICKENS WITH INCREASED MHC-CHROMOSOME DOSAGES

Increased dosage of genes belonging to the immunoglobulin superfamily may be responsible for some of the less noticeable but targeted phenotypic disturbances seen in trisomy conditions of humans and animals. We used an avian aneuploidy model to study the specific effects of extra major histocompatibility complex (MHC)-microchromosome dosage on the progression of thymocyte differentiation through a broad period of embryonic and neonatal development. The particular goal in the present investigation was to determine whether a reduction in the number of thymocytes, previously observed in the developing thymus of MHC aneuploids, is accompanied by particular alterations in thymocyte differentiation. We hypothesized that the subpopulation structure and/or developmental pattern for thymocyte differentiation are characteristically perturbed (delayed or modified) by increased MHC-chromosome dosage in cells. The regulation of MHC surface antigen expression in aneuploid thymocytes was also studied to detect dosage-dependent expression for one and possibly more sub-regions (class I, II, IV) of the avian MHC. Surface densities of MHC class I antigens on thymocytes were increased significantly at all ages studied, for example by 15% and 45% in trisomics and tetrasomics, respectively at 22 days post-hatching. The surface density of CT1 antigen, a thymocyte-specific marker, was also increased in a dosage-dependent manner, but only in juveniles. Increases in the proportion of alpha beta(1) TCR(+) and CD3(+) thymocytes were observed in juveniles, with no alterations in other TCR-expressing thymocytes. No major alterations in CD4 and CD8 thymocyte populations were observed. These results demonstrate a targeted effect of extra MHC-chromosome dosage towards enhanced class I and CT1, and not class II or IV, expression. The increased MHC-microchromosome dosage appears to influence primarily immature thymocytes expressing alpha beta(1) TCR and CD3.