λ Light Chain Bias Associated With Enhanced Binding and Function of Anti-HIV Env Glycoprotein Antibodies.
The humoral response to human immunodeficiency virus (HIV) remains incompletely understood. In this report, we describe biased λ light chain use during the HIV Env glycoprotein (Env) response in HIV infection and vaccination. We examined HIV Env binding (and neutralization) in the context of light chain use in subjects with acute HIV infection, chronic HIV infection, and among HIV vaccinees. In all populations tested, there was a λ chain bias for HIV Env binding antibodies, compared with other HIV antigens (such as p24) or tetanus toxoid. In subjects with chronic HIV infection, a λ bias was noted for neutralization, with λ antibodies accounting for up to 90% of all neutralization activity observed. This is the first report of antibody function in a human infection being tied to light chain use. In HIV infection, antibodies expressing λ light chains tended to have longer CDRL3s, increased light chain contact with HIV Env, and less hypermutation in the heavy chain, compared with antibodies using the κ light chain. These data also support an evolutionary model for the understanding the various κ to λ light chain ratios observed across species and suggest that the λ light chain bias against HIV provides the host an advantage in developing a more efficient humoral response.
Institute of Human Virology, University of Maryland School of Medicine Department of Medicine, Baltimore VA Medical Center, Maryland.
Mohammad M
MM
Sajadi
Institute of Human Virology, University of Maryland School of Medicine.
Maham
M
Farshidpour
Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
Eric P
EP
Brown
Institute of Human Virology, University of Maryland School of Medicine.
Xin
X
Ouyang
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Michael S
MS
Seaman
Institute of Human Virology, University of Maryland School of Medicine.
Marzena
M
Pazgier
Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
Margaret E
ME
Ackerman
GeoVax, Atlanta, Georgia.
Harriet
H
Robinson
Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina.
Georgia
G
Tomaras
Department of Microbiology and Immunology, University of Melbourne, Australia.
Matthew S
MS
Parsons
Institute of Human Virology, University of Maryland School of Medicine.
Manhattan
M
Charurat
Institute of Human Virology, University of Maryland School of Medicine.
Anthony L
AL
DeVico
Institute of Human Virology, University of Maryland School of Medicine.
Robert R
RR
Redfield
Institute of Human Virology, University of Maryland School of Medicine.
George K
GK
Lewis
D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral; D007147:Immunoglobulin Light Chains / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D055815:Young Adult; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D007147:Immunoglobulin Light Chains; D054299:env Gene Products, Human Immunodeficiency Virus
HIV; antibody; humoral immunity; light chain; neutralization