       Document 0126
 DOCN  M95B0126
 TI    Analysis of human monoclonal antibodies elicited by vaccination with a
       Cryptococcus neoformans glucuronoxylomannan capsular polysaccharide
       vaccine.
 DT    9511
 AU    Pirofski L; Lui R; DeShaw M; Kressel AB; Zhong Z; Department of
       Microbiology, Albert Einstein College of Medicine,; Bronx, New York
       10461, USA.
 SO    Infect Immun. 1995 Aug;63(8):3005-14. Unique Identifier : AIDSLINE
       GENBANK/U27190
 AB    The Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan
       (GXM) has been conjugated to tetanus toxoid (GXM-TT) as an
       investigational vaccine. GXM-TT elicits antibodies that are protective
       in C. neoformans-infected mice. In an effort to characterize the fine
       specificity and molecular structure of human GXM-TT-elicited antibodies,
       we generated two GXM monoclonal antibodies (MAbs) from peripheral blood
       lymphocytes of a volunteer GXM-TT recipient and studied serum GXM
       antibody idiotype expression in 10 additional vaccinees. The MAbs, 2E9
       and 3B6, are the immunoglobulin M(lambda) isotype and bind capsular
       polysaccharides of C. neoformans serotypes other than the serotype A
       that was used for immunization. Neither antibody competes with murine
       GXM MAbs for antigen binding, suggesting that the human MAbs recognize a
       different epitope. The B-cell superantigen staphylococcal protein A
       binds both MAbs, and human immunodeficiency virus gp120 binds 2E9. MAb
       nucleic acid sequence analysis revealed that both antibodies use an
       identical V lambda 1a-J lambda genetic element with different,
       somatically mutated, members of the VH3 gene family and different DH and
       JH gene elements. The gene elements used by both MAbs occur in fetal
       B-lymphocyte repertoires, autoantibodies, and other polysaccharide
       antibodies. Post-GXM-TT vaccination GXM antibodies from 10 additional
       vaccinees expressed a shared idiotype defined by rabbit antiserum raised
       against MAb 2E9. Our data suggest that the human GXM antibody response
       is restricted and raise questions regarding the importance of specific
       variable-region elements and superantigens in the generation of human
       antibody responses to encapsulated pathogens.
 DE    Amino Acid Sequence  Antibodies, Fungal/*IMMUNOLOGY  Antibodies,
       Monoclonal/*IMMUNOLOGY  Antibody Specificity  Antigens,
       Fungal/IMMUNOLOGY  Base Sequence  Comparative Study  Cryptococcus
       neoformans/*IMMUNOLOGY  Fungal Vaccines/IMMUNOLOGY  Genes,
       Immunoglobulin  Human  Immunoglobulin Idiotypes/IMMUNOLOGY
       Immunoglobulin Variable Region/GENETICS  Isoelectric Point  Molecular
       Sequence Data  Polysaccharides/*IMMUNOLOGY  Sequence Alignment  Sequence
       Homology, Amino Acid  Sequence Homology, Nucleic Acid  Support, U.S.
       Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

