title: Comparison of antibody repertoires produced by HIV-1 infection, other chronic and acute infections, and systemic autoimmune disease.
abstract: BACKGROUND
  Antibodies (Abs) produced during HIV-1 infection rarely neutralize a broad range of viral isolates; only eight broadly-neutralizing (bNt) monoclonal (M)Abs have been isolated. Yet, to be effective, an HIV-1 vaccine may have to elicit the essential features of these MAbs. The V genes of all of these bNt MAbs are highly somatically mutated, and the V(H) genes of five of them encode a long (≥ 20 aa) third complementarity-determining region (CDR-H3). This led us to question whether long CDR-H3s and high levels of somatic mutation (SM) are a preferred feature of anti-HIV bNt MAbs, or if other adaptive immune responses elicit them in general.
  
  
  RESULTS
  We assembled a V(H)-gene sequence database from over 700 human MAbs of known antigen specificity isolated from chronic (viral) infections (ChI), acute (bacterial and viral) infections (AcI), and systemic autoimmune diseases (SAD), and compared their CDR-H3 length, number of SMs and germline V(H)-gene usage. We found that anti-HIV Abs, regardless of their neutralization breadth, tended to have long CDR-H3s and high numbers of SMs. However, these features were also common among Abs associated with other chronic viral infections. In contrast, Abs from acute viral infections (but not bacterial infections) tended to have relatively short CDR-H3s and a low number of SMs, whereas SAD Abs were generally intermediate in CDR-H3 length and number of SMs. Analysis of V(H) gene usage showed that ChI Abs also tended to favor distal germline V(H)-genes (particularly V(H)1-69), especially in Abs bearing long CDR-H3s.
  
  
  CONCLUSIONS
  The striking difference between the Abs produced during chronic vs. acute viral infection suggests that Abs bearing long CDR-H3s, high levels of SM and V(H)1-69 gene usage may be preferentially selected during persistent infection.
authors.affiliation: Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada. breden@sfu.ca
authors.forename: Felix
authors.initials: F
authors.lastname: Breden
authors.forename: Christa
authors.initials: C
authors.lastname: Lepik
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Longo
authors.forename: Marinieve
authors.initials: M
authors.lastname: Montero
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
authors.forename: Jamie K
authors.initials: JK
authors.lastname: Scott
mesh_terms: D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000235:genetics; D000917:Antibody Formation / Q000235:genetics; D001327:Autoimmune Diseases / Q000150:complications* / Q000276:immunology*; D002908:Chronic Disease; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005786:Gene Expression Regulation; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D009154:Mutation / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions; D000939:Epitopes; D015483:HIV Antibodies; D007143:Immunoglobulin Heavy Chains