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

Increased dosage of genes belonging to the immunoglobulin superfamily may be responsible for some of the less noticeable but targeted phenot ypic 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 emb ryonic and neonatal development. The particular goal in the present in vestigation was to determine whether a reduction in the number of thym ocytes, previously observed in the developing thymus of MHC aneuploids , is accompanied by particular alterations in thymocyte differentiatio n. We hypothesized that the subpopulation structure and/or development al pattern for thymocyte differentiation are characteristically pertur bed (delayed or modified) by increased MHC-chromosome dosage in cells. The regulation of MHC surface antigen expression in aneuploid thymocy tes 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 signif icantly at all ages studied, for example by 15% and 45% in trisomics a nd tetrasomics, respectively at 22 days post-hatching. The surface den sity of CT1 antigen, a thymocyte-specific marker, was also increased i n a dosage-dependent manner, but only in juveniles. Increases in the p roportion 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 observe d. These results demonstrate a targeted effect of extra MHC-chromosome dosage towards enhanced class I and CT1, and not class II or IV, expr ession. The increased MHC-microchromosome dosage appears to influence primarily immature thymocytes expressing alpha beta(1) TCR and CD3.