GENETIC CONTROL OF THE IMMUNE RESPONSE TO HAEMOGLOBIN: III. VARIANT A_β (bm 12) BUT NOT A_e (D2.GD) Ia POLYPEPTIDES ALTER IMMUNE RESPONSIVENESS TOWARDS THE α‐SUBUNIT OF HUMAN HAEMOGLOBIN

Mice bearing the I‐A subregion mutation bm12 were immunized and challenged with the α‐subunit of human adult haemoglobin. Under conditions in which parental B6/Kh mice respond, B6.C‐H‐2^bm12 mice are inhibited nearly 100% in their ability to respond to challenge to the α‐chain of haemoglobin. D2.GD mice which express a variant A_e (E_β) polypeptide of the I‐E subregion can respond as well as B10.D2 mice to both subunits (α‐ and β‐) of haemoglobin. These observations as well as other genetic mapping data confirm the I‐A mapping of α‐chain‐specific Ir genes and extend the genetic fine mapping to the A_β gene within the I‐A subregion or a combinatorial Ia determinant generated by an interaction of A_α and A_β. In addition they implicate the Ia.8 specificity in determining immune responsiveness to α‐chain determinants.