Antigen nature and complexity influence human antibody light chain usage and specificity.
Human antibodies consist of a heavy chain and one of two possible light chains, kappa (κ) or lambda (λ). Here we tested how these two possible light chains influence the overall antibody response to polysaccharide and protein antigens by measuring light chain usage in human monoclonal antibodies from antibody secreting cells obtained following vaccination with Pneumovax23. Remarkably, we found that individuals displayed restricted light chain usage to certain serotypes and that lambda antibodies have different specificities and modes of cross-reactivity than kappa antibodies. Thus, at both the monoclonal (7 kappa, no lambda) and serum levels (145μg/mL kappa, 2.82μg/mL lambda), antibodies to cell wall polysaccharide were nearly always kappa. The pneumococcal reference serum 007sp was analyzed for light chain usage to 12 pneumococcal serotypes for which it is well characterized. Similar to results at the monoclonal level, certain serotypes tended to favor one of the light chains (14 and 19A, lambda; 6A and 23F, kappa). We also explored differences in light chain usage at the serum level to a variety of antigens. We examined serum antibodies to diphtheria toxin mutant CRM197 and Epstein-Barr virus protein EBNA-1. These responses tended to be kappa dominant (average kappa-to-lambda ratios of 4.52 and 9.72 respectively). Responses to the influenza vaccine were more balanced with kappa-to-lambda ratio averages having slight strain variations: seasonal H1N1, 1.1; H3N2, 0.96; B, 0.91. We conclude that antigens with limited epitopes tend to produce antibodies with restricted light chain usage and that in most individuals, antibodies with lambda light chains have specificities different and complementary to kappa-containing antibodies.
Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA. Electronic address: Kenneth-Smith@omrf.org.
Kenneth
K
Smith
Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA; Pamlico BioPharma Inc., 865 Research Parkway, Suite 400, Oklahoma City, OK 73104, USA.
Hemangi
H
Shah
Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA.
Jennifer J
JJ
Muther
Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA.
Angie L
AL
Duke
Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA.
Kathleen
K
Haley
Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA; Oklahoma University Health Science Center, 1100 N. Lindsay, Oklahoma City, OK 73104, USA.
Judith A
JA
James
D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity; D001426:Bacterial Proteins / Q000276:immunology; D003429:Cross Reactions; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D004854:Herpesvirus 4, Human; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype; D053122:Influenza A Virus, H3N2 Subtype; D007252:Influenza Vaccines / Q000276:immunology; D022242:Pneumococcal Vaccines / Q000276:immunology
C414006:23-valent pneumococcal capsular polysaccharide vaccine; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D001426:Bacterial Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D007252:Influenza Vaccines; D022242:Pneumococcal Vaccines; C028581:CRM197 (non-toxic variant of diphtheria toxin); C417029:EBV-encoded nuclear antigen 1
Anti-polysaccharide; Human monoclonal antibodies; Kappa light chain; Lambda light chain; Light chain usage