Major histocompatibility complex phenotypes influence serum testosterone concentration.

Objectives: (a) To confirm our earlier observation that the phenotype HLA-DR4,7 occurs with higher frequency in male patients with rheumatoid arthritis (RA) than in female patients. (b) To test the hypothesis that DR7 is associated with low normal serum testosterone (Te) levels in healthy males; this might explain the increased frequency of DR4,7 in male patients since there appears to be a relationship between low serum Te and RA. (c) To characterize the association between HLA alleles and serum Te concentration in healthy males.

Evidence showing that the 1105 and 1106 isotypic residues of the fourth component of human complement, C4A, are not involved in amide bond formation.

Human C4A and C4B have different functions that may stem from their ability to bind hydroxyl or free amino groups on complement activating surfaces. Previous studies suggest that C4B binds to hydroxyl or amino groups whereas C4A binds to free amino groups on acceptor molecules. Comparison of the derived amino acid sequences of C4A and C4B has shown that differences exist between them at positions 1101, 1102, 1105 and 1106.

Amino acid residues 1101-1105 of the isotypic region of human C4B is important to the covalent binding activity of complement component C4.

The C4A and C4B isotypes of human C4 show certain functional differences that stem from their relative preference for transacylation to amino (-NH2) vs hydroxyl (-OH) nucleophiles, respectively, on complement-activating surfaces. Comparison of amino acid sequences of the alpha-chain fragment of C4, C4d, has shown C4A- and C4B-specific sequences at residues 1101-1106 are the only consistent structural difference between isotype, i.e.

Monoclonal antipeptide antibodies against amino acid residues 1101-1106 of human C4 distinguish C4A from C4B.

Comparison of amino acid sequences of the alpha-chain fragment of human C4, C4d, has shown C4A- and C4B-specific sequences at residues 1101-1106 in which the aspartic acid-histidine substitution at position 1106 may be related to the amide and ester bond forming properties of these molecules. Peptides containing twelve amino acid residues of the C4A- or C4B-specific sequences were synthesized and injected into female Balb/c mice. Serum from 2 mice, one immunized with the C4A-specific peptide and the other with the C4B-specific peptide, gave strong isotype-specific responses in an enzyme-linked immunosorbent assay against affinity-purified C4A3 and C4B2B1.

The fluid-phase binding of human C4 and its genetic variants, C4A3 and C4B1, to immunoglobulins.

Covalent binding of the fourth complement protein, C4, to immune complexes is an important first step in the complement mediated processing of the complexes. Many of the initial encounters between the proteins of the complement system and antigen and antibody occur in solution, and prior to this report, studies of the interactions between them have focused on complement binding to preformed immune precipitates that most likely are not found in vivo. We have characterized the covalent binding of C4b to immunoglobulin molecules in a fluid-phase system consisting only of antibody in solution and purified C4 and C1s.