title: HIV-1 Tat-specific IgG antibodies in high-responders target a B-cell epitope in the cysteine-rich domain and block extracellular Tat efficiently.
abstract: Tat, an important regulatory protein of HIV-1, has been implicated in HIV-related pathogenesis. Immune responses to Tat, although underrepresented, confer protection against disease progression, in natural infection and experimental immunization, making Tat an attractive vaccine candidate. Information on immune responses to Tat from India which has the second largest HIV incidence has been lacking. Here we report a cross-sectional study evaluating the humoral response to Tat from a large number of samples from two southern states of India. 14% of the seropositive (63/447) and 4.6% of seronegative samples (7/150) harbored Tat-reactive antibodies. A significant number of the seropositive samples contained high levels of anti-Tat antibodies (31/447) which demonstrated class-switch to IgG1 and bound to Tat with high avidity. Cross-reactivity analysis showed that these antibodies interacted with Tat from different clades with variable degree with the highest interaction with subtype-AE and the least with subtype-B Tat. Importantly, a B-cell epitope in the cysteine-rich domain was found to be the most immunodominant one and antibodies interacting with this epitope blocked extracellular Tat efficiently. To the best of our knowledge this is the first report on immune responses to Tat from Indian populations and the data presented here could significantly contribute to HIV Tat vaccine design.
authors.affiliation: Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560 064, India.
authors.forename: Venkatesh Prasanna
authors.initials: VP
authors.lastname: Kashi
authors.forename: Rajesh Abraham
authors.initials: RA
authors.lastname: Jacob
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Paul
authors.forename: Kaustuv
authors.initials: K
authors.lastname: Nayak
authors.forename: Bhuthiah
authors.initials: B
authors.lastname: Satish
authors.forename: Soumya
authors.initials: S
authors.lastname: Swaminathan
authors.forename: Kadappa S
authors.initials: KS
authors.lastname: Satish
authors.forename: Udaykumar
authors.initials: U
authors.lastname: Ranga
mesh_terms: D000293:Adolescent; D000328:Adult; D000915:Antibody Affinity; D003429:Cross Reactions; D003430:Cross-Sectional Studies; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006679:HIV Seropositivity; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral; D016056:Immunodominant Epitopes; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D007194:India; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D055815:Young Adult; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D018985:Epitopes, B-Lymphocyte; D015483:HIV Antibodies; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D054322:tat Gene Products, Human Immunodeficiency Virus