Infection with Human Immunodeficiency Virus Type I (HIV-1) and Human T Cell Lymphotropic Viruses among Leprosy Patients and Contacts: Correlation between HIV-1 Cross-Reactivity and Antibodies to Lipoarabinomannan

ABSTRACT The relative contributions of HLA alleles and T-cell receptors (TCRs) to the prevention of mutational viral escape are unclear. Here, we examined human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T-cell responses restricted by two closely related HLA class I alleles, B*5701 and B*5703, that differ by two amino acids but are both associated with a dominant response to the same HIV-1 Gag epitope KF11 (KAFSPEVIPMF). When this epitope is presented by HLA-B*5701, it induces a TCR repertoire that is highly conserved among individuals, cross-recognizes viral epitope variants, and is rarely associated with mutational escape. In contrast, KF11 presented by HLA-B*5703 induces an entirely different, more heterogeneous TCR β-chain repertoire that fails to recognize specific KF11 escape variants which frequently arise in clade C-infected HLA-B*5703+ individuals. These data show the influence of HLA allele subtypes on TCR selection and indicate that extensive TCR diversity is not a prerequisite to prevention of allowable viral mutations.

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Enhanced immunogenicity using an alphavirus replicon DNA vaccine against human immunodeficiency virus type 1

Journal of General Virology ◽

10.1099/vir.0.80481-0 ◽

2005 ◽

Vol 86 (2) ◽

pp. 349-354 ◽

Cited By ~ 35

Author(s):

Eva K. L. Nordström ◽

Mattias N. E. Forsell ◽

Christina Barnfield ◽

Eivor Bonin ◽

Tomas Hanke ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Dna Vaccine ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Semliki Forest Virus ◽

Cell Responses ◽

Immunodeficiency Virus ◽

Hiv 1

With the human immunodeficiency virus type 1 (HIV-1) epidemic expanding at increasing speed, development of a safe and effective vaccine remains a high priority. One of the most central vaccine platforms considered is plasmid DNA. However, high doses of DNA and several immunizations are typically needed to achieve detectable T-cell responses. In this study, a Semliki Forest virus replicon DNA vaccine designed for human clinical trials, DREP.HIVA, encoding an antigen that is currently being used in human trials in the context of a conventional DNA plasmid, pTHr.HIVA, was generated. It was shown that a single immunization of DREP.HIVA stimulated HIV-1-specific T-cell responses in mice, suggesting that the poor immunogenicity of conventional DNA vaccines may be enhanced by using viral replicon-based plasmid systems. The results presented here support the evaluation of Semliki Forest virus replicon DNA vaccines in non-human primates and in clinical studies.

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Ontogeny and Specificities of Mucosal and Blood Human Immunodeficiency Virus Type 1-Specific CD8+ Cytotoxic T Lymphocytes

Journal of Virology ◽

10.1128/jvi.77.1.291-300.2003 ◽

2003 ◽

Vol 77 (1) ◽

pp. 291-300 ◽

Cited By ~ 46

Author(s):

L. Musey ◽

Y. Ding ◽

J. Cao ◽

J. Lee ◽

C. Galloway ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cytotoxic T Lymphocyte ◽

Infected Individual ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Induction of adaptive immunity to human immunodeficiency virus type 1 (HIV-1) at the mucosal site of transmission is poorly understood but crucial in devising strategies to control and prevent infection. To gain further understanding of HIV-1-specific T-cell mucosal immunity, we established HIV-1-specific CD8+ cytotoxic T-lymphocyte (CTL) cell lines and clones from the blood, cervix, rectum, and semen of 12 HIV-1-infected individuals and compared their specificities, cytolytic function, and T-cell receptor (TCR) clonotypes. Blood and mucosal CD8+ CTL had common HIV-1 epitope specificities and major histocompatibility complex restriction patterns. Moreover, both systemic and mucosal CTL lysed targets with similar efficiency, primarily through the perforin-dependent pathway in in vitro studies. Sequence analysis of the TCRβ VDJ region revealed in some cases identical HIV-1-specific CTL clones in different compartments in the same HIV-1-infected individual. These results clearly establish that a subset of blood and mucosal HIV-1-specific CTL can have a common origin and can traffic between anatomically distinct compartments. Thus, these effectors can provide immune surveillance at the mucosa, where rapid responses are needed to contain HIV-1 infection.

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