V[sub H] restriction among human cold agglutinins: The V[sub H]4-21 gene segment is required to encode anti-I and anti-I specificities

Journal Article · Thu Oct 01 04:00:00 EDT 1992 · Journal of Immunology; (United States)

OSTI ID:7009681

Pascual, V; Victor, K; Capra, J D ^[1]; Spellerberg, M; Hamblin, T J; Stevenson, F K ^[2]

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1. Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)
2. General Hospital, Southampton (United Kingdom)

The authors previously reported that human autoantibodies with cold agglutinin activity contained a single human V[sub H] gene segment (V[sub H]4-21) which was also responsible for the cross-idiotypic specificity characteristic of the cold agglutinin response. To confirm and extend this observation they have analyzed at the nucleotide level the H and L chains of six new cold agglutinin molecules derived from different patients. They found that regardless of whether the antibody recognizes the i or the I red cell Ag, restriction at the V[sub H] gene segment level is absolute. They also found that even in the absence of somatic mutation the V[sub H]4-21 gene segment can encode both anti-i and anti-I specificities. Finally, although the V[sub H]4-21 gene segment is essential for cold agglutinin activity, the other genetic elements that contribute to the V region of the antibody molecules can be extremely diverse. The structural information provided in this report sharply restricts the requirement for encoding pathogenic cold agglutinin activity to one of the components of the H chain V region, specifically the V[sub H] gene segment. The implications of this apparently absolute requirement for a single V[sub H] gene segment, unprecedented in the human autoimmune response, are discussed. 55 refs., 5 figs., 3 tabs.

• OSTI ID: 7009681
• Journal Information: Journal of Immunology; (United States), Journal Name: Journal of Immunology; (United States) Vol. 149:7; ISSN 0022-1767; ISSN JOIMA3
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
GENE REGULATION
GLOBULINS
IMMUNE REACTIONS
IMMUNOGLOBULINS
ORGANIC COMPOUNDS
PROTEINS