Unusual genes at the aminoterminus of human immunoglobulin variants

Abstract

HEAVY chain disease proteins^1–3 are defective immunoglobulin molecules caused by a mutation of heavy chain structural genes. Defective γ, α, and μ chains have been described in man, and a few abnormal myeloma proteins have been identified in the mouse⁴. In general the variants are shorter than their normal counterparts because of terminal or internal deletions. The deletions can affect either the constant (C) genes, or both the C and variable (V) genes. When the mutation affects C genes, the defect seems not to be random, as it generally involves either intact domains and/or interdomain regions³. On the other hand, V gene deletions seem not only to be random in location and size, but in some instances to have distinct features such as unusual amino acid sequences and/or the presence of carbohydrate moieties in unusual sites⁵. We present here studies of the aminoterminal regions of two new heavy chain disease proteins (HAR and LEA)⁶ and more quantitative data on certain ambiguities of a third protein (CRA) which has been partially sequenced⁵. Table 1 lists some physicochemical properties (details will be published elsewhere) of heavy chain disease proteins LEA, HAR and CRA.