ISSN:0883-0185    

DOI:10.3109/08830189209061779

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189209061780

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Human antibody to the Haemophilus influenzae capsular polysaccharide (Hib CP) is restricted in diversity in the individual and the population with a limited number of variable region genes encoding antibody. Antibody to the Hib CP shows restricted isoelectric focusing gel patterns and light chain usage with frequent restriction to use of only kappa light chains. Shared cross-reactive idiotypes are expressed on antibody. The heavy chain of antibody to the Hib CP is predominantly encoded by two members of the VH3family—LSG 6.1/M85-like and VH26/30P1-like. In VHthe CDR1, based on complete identity in LSG 6.1/M85-like antibodies, CDR2, based on the suggestion of mutation in this region, and CDR3, based on conserved CDR3 usage in unrelated individuals, may be important for antigen binding. Six or more different VLgene families encode antibody. The predominant antibody of the majority of individuals uses the A2-VκII gene in germline or near germline configuraion, which encodes an idiotype designated Hibld-1. Antibody can also be encoded by VκI, non-A2 VκII, VκIII, VκIV, VλII, and VλVII genes. Although different VLgenes can be used, unrelated individuals appear to use the same VκIII (A27), VλII (Vλ2.1 and VλVII (4A) genes. The VLdiversity accounts for differences in fine binding specificity, with A2-VλII genes not encodingE. coliK100 CP cross-reactive antibodies and VλVII genes and some of the non-A2 Vκgenes encoding cross-reactive antibodies. The arginine in CDR3 of both antibody kappa and lambda light chains and the asparagine in CDR2 of VLsequences and in CDR1 of LSG6.1-M85 VHsequences of antibody appear to be important residues for antigen binding. A relatively limited degree of somatic mutation has occurred in the non-A2 VLgenes, VλVII, and the VHgenes. Further studies comparing the polymorphism of germline V genes to antibody-encoding V genes are needed to clarify this issue. Research comparing this repertoire to repertoires directed to other bacterial CP and to self antigens and defining structure-antigen binding relationships is in progress.

ISSN:0883-0185    

DOI:10.3109/08830189209061781

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The V region repertoire of the human antibody response to the type b capsular polysaccharide of Haemophilus influenzae (Hib-PS) is being defined at the molecular level using antibodies purified from serum of immunized adults. The VH of this response is restricted to the VHIII subgroup while the VL can be divided into two categories. The most common VL, expressed in>90% of adults and usually constituting the majority of a subjects anti-Hib-PS antibody response, is restricted to the product of a single VκII gene known as A2 that probably lacks somatic mutations. The product of the A2 gene is invariably joined to one of several JK products by an inserted arginine at the Vκ-Jκjunction. In contrast to the restricted nature of the dominant VL clonotype, the second category of VL constitutes a heterogeneous group of at least seven different VL gene products that often contain somatic mutations and generally exhibit crossreactivity with a related polysaccharide fromE. coli.Elucidation of anti-Hib-PS V regions at the molecular level will permit examination of structure-function relationships among these clinically important antibodies and should make the V region repertoire to Hib-PS a useful model for studying human V gene responses.

ISSN:0883-0185    

DOI:10.3109/08830189209061782

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

We have investigated the human antibody repertoires that bind to two different classes of bacterial antigens. Immunization with the conventional antigen, type b capsular polysaccharide of Haemophilus influenzae Hib PS, uniformly induces IgA and IgG responses dominated by clones that use heavy chains structurally related to two subsets of VH3genes, while in a minority of subjects antibodies from the VH1 or VH4 families are co-induced. In contrast, the“alternative binding site”of Staphylococcal Protein A (SPA) represents an unconventional determinant, because; (i) SPA is bound by a large proportion of non-immune IgM, IgA and IgG F(ab')2, (ii) SPA is bound only to Fab from the VH3 family, which can be encoded by at least four different germline genes, (iii) SPA binding is independent of VLusage, (iv) by flow cytometry SPA is bound by>15% of tonsilar B cells, but not to T cells, (v)In vitrostimulation with an SPA containing mitogen induces the preferentially production of Ig bearing a VH3 marker. Taken together, these studies characterize a VHfamily restricted binding interaction that is distinct from the properties associated with conventional antigens such as Hib PS. Based on these data we propose that SPA represents a prototype for a B cell superantigen.

ISSN:0883-0185    

DOI:10.3109/08830189209061783

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189209061778

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor