Genetic control of the immune response to human adult haemoglobin (HbA1) and sickle cell haemoglobin (HbS).

Abstract

The humoral response of twelve strains of mice to immunization with either normal adult human haemoglobin (HbA1) or sickle-cell haemoglobin (HbS) was studied using a quantitative enzyme-linked immunosorbant assay (ELISA). Results indicate the presence of at least two genes that control the magnitude of this response, one of which is located at the 'D-end' of the H-2 complex. H-2 haplotypes s, q and k are associated with a low response, haplotypes d and a with a high response, and the b haplotype with an intermediate response. No difference in the pattern or magnitude of the response was observed when HbS was used as the immunogen in place of HbA1. The N-terminal octapeptides of the beta chains of HbA1 and HbS were synthesized and the presence of antibodies specific for the N-terminal octapeptides was tested. The magnitude of the anti-N-terminal response correlated with that to the intact molecules with one exception. A much lower response to the beta s-peptide was found in the C57BL/10Sn mice. Monoclonal antibodies were prepared to HbA1 and HbS. Three clones were studied for their reaction with HbA1, HbS, and the beta A1 and beta S peptides. One clone was found which binds both the beta A1 and beta S peptides. This indicates that the N-terminal portion of the beta chain of human haemoglobin is antigenic in mice.