scholarly journals HLA-B63 Presents HLA-B57/B58-Restricted Cytotoxic T-Lymphocyte Epitopes and Is Associated with Low Human Immunodeficiency Virus Load

2005 ◽  
Vol 79 (16) ◽  
pp. 10218-10225 ◽  
Author(s):  
Nicole Frahm ◽  
Sharon Adams ◽  
Photini Kiepiela ◽  
Caitlyn H. Linde ◽  
Hannah S. Hewitt ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Disease Progression ◽  
Hla Class I ◽  
Class I ◽  
Binding Motif ◽  
Hiv Disease ◽  
Hiv Replication ◽  
Immune Correlates ◽  
Immunodeficiency Virus

ABSTRACT Several HLA class I alleles have been associated with slow human immunodeficiency virus (HIV) disease progression, supporting the important role HLA class I-restricted cytotoxic T lymphocytes (CTL) play in controlling HIV infection. HLA-B63, the serological marker for the closely related HLA-B*1516 and HLA-B*1517 alleles, shares the epitope binding motif of HLA-B57 and HLA-B58, two alleles that have been associated with slow HIV disease progression. We investigated whether HIV-infected individuals who express HLA-B63 generate CTL responses that are comparable in breadth and specificity to those of HLA-B57/58-positive subjects and whether HLA-B63-positive individuals would also present with lower viral set points than the general population. The data show that HLA-B63-positive individuals indeed mounted responses to previously identified HLA-B57-restricted epitopes as well as towards novel, HLA-B63-restricted CTL targets that, in turn, can be presented by HLA-B57 and HLA-B58. HLA-B63-positive subjects generated these responses early in acute HIV infection and were able to control HIV replication in the absence of antiretroviral treatment with a median viral load of 3,280 RNA copies/ml. The data support an important role of the presented epitope in mediating relative control of HIV replication and help to better define immune correlates of controlled HIV infection.

Human immunodeficiency virus (HIV) infection

2011 ◽  
pp. 663-669
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Opportunistic Infections ◽  
Tissue Loss ◽  
Atherosclerotic Cardiovascular Disease ◽  
Hiv Disease ◽  
Hiv Replication ◽  
Pharmacological Management ◽  
Nutritional Conditions ◽  
Immunodeficiency Virus

Introduction, nutritional goals, and assessment 664 Unintentional weight and lean tissue loss 666 Cardiovascular risk and complications associated with HIV disease and treatment 667 Additional dietary issues 668 Untreated human immunodeficiency virus (HIV) infection leads to progressive suppression of immune function, eventually rendering the body susceptible to opportunistic infections and tumours. While there is no cure, antiretroviral therapy (ART) is highly effective in suppressing HIV replication. HIV disease is now a chronic condition and causes of death in this population have shifted from traditional AIDS-related illnesses to non-AIDS (Acquired Immune Deficiency Syndrome) events, the most common being atherosclerotic cardiovascular disease, liver disease, end-stage renal disease and non-AIDS–defining malignancies. There are a diverse range of nutritional conditions associated with HIV, reflecting the complexity of the disease and pharmacological management....

HLA Class I Homozygosity Accelerates Disease Progression in Human Immunodeficiency Virus Type 1 Infection

1999 ◽  
Vol 15 (4) ◽  
pp. 317-324 ◽  
Author(s):  
Jianming Tang ◽  
Caroline Costello ◽  
Ireneus P.M. Keet ◽  
Charles Rivers ◽  
Susan Leblanc ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Disease Progression ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Hla Class I ◽  
Class I ◽  
Immunodeficiency Virus

scholarly journals Effective T-Cell Responses Select Human Immunodeficiency Virus Mutants and Slow Disease Progression

2007 ◽  
Vol 81 (12) ◽  
pp. 6742-6751 ◽  
Author(s):  
A. J. Frater ◽  
H. Brown ◽  
A. Oxenius ◽  
H. F. Günthard ◽  
B. Hirschel ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Disease Progression ◽  
T Cell Responses ◽  
Hla Class I ◽  
Class I ◽  
Cell Responses ◽  
Hla Class I Molecules ◽  
Immunodeficiency Virus ◽  
African Patients

ABSTRACT The possession of some HLA class I molecules is associated with delayed progression to AIDS. The mechanism behind this beneficial effect is unclear. We tested the idea that cytotoxic T-cell responses restricted by advantageous HLA class I molecules impose stronger selection pressures than those restricted by other HLA class I alleles. As a measure of the selection pressure imposed by HLA class I alleles, we determined the extent of HLA class I-associated epitope variation in a cohort of European human immunodeficiency virus (HIV)-positive individuals (n = 84). We validated our findings in a second, distinct cohort of African patients (n = 516). We found that key HIV epitopes restricted by advantageous HLA molecules (B27, B57, and B51 in European patients and B5703, B5801, and B8101 in African patients) were more frequently mutated in individuals bearing the restricting HLA than in those who lacked the restricting HLA class I molecule. HLA alleles associated with clinical benefit restricted certain epitopes for which the consensus peptides were frequently recognized by the immune response despite the circulating virus's being highly polymorphic. We found a significant inverse correlation between the HLA-associated hazard of disease progression and the mean HLA-associated prevalence of mutations within epitopes (P = 0.028; R 2 = 0.34). We conclude that beneficial HLA class I alleles impose strong selection at key epitopes. This is revealed by the frequent association between effective T-cell responses and circulating viral escape mutants and the rarity of these variants in patients who lack these favorable HLA class I molecules, suggesting a significant pressure to revert.

scholarly journals Markers predicting progression of human immunodeficiency virus-related disease.

1994 ◽  
Vol 7 (1) ◽  
pp. 14-28 ◽  
Author(s):  
C M Tsoukas ◽  
N F Bernard
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune System ◽  
Hiv Infection ◽  
Disease Progression ◽  
Opportunistic Infections ◽  
Surrogate Marker ◽  
Disease Process ◽  
Surrogate Markers ◽  
Hiv Disease ◽  
Immunodeficiency Virus

Human immunodeficiency virus (HIV) interacts with the immune system throughout the course of infection. For most of the disease process, HIV activates the immune system, and the degree of activation can be assessed by measuring serum levels of molecules such as beta 2-microglobulin and neopterin, as well as other serum and cell surface phenotype markers. The levels of some of these markers correlate with clinical progression of HIV disease, and these markers may be useful as surrogate markers for development of clinical AIDS. Because the likelihood and timing of development of clinical AIDS following seroconversion, for any particular individual, are not readily predictable, the use of nonclinical disease markers has become critically important to patient management. Surrogate markers of HIV infection are, by definition, measurable traits that correlate with disease progression. An ideal marker should identify patients at highest risk of disease progression, provide information on how long an individual has been infected, help in staging HIV disease, predict development of opportunistic infections associated with AIDS, monitor the therapeutic efficacy of immunomodulating or antiviral treatments, and the easily quantifiable, reliable, clinically available, and affordable. This review examines the current state of knowledge and the role of surrogate markers in the natural history and treatment of HIV infection. The clinical usefulness of each marker is assessed with respect to the criteria outlined for the ideal surrogate marker for HIV disease progression.

scholarly journals Impact of HLA in Mother and Child on Disease Progression of Pediatric Human Immunodeficiency Virus Type 1 Infection

2009 ◽  
Vol 83 (19) ◽  
pp. 10234-10244 ◽  
Author(s):  
Christina F. Thobakgale ◽  
Andrew Prendergast ◽  
Hayley Crawford ◽  
Nompumelelo Mkhwanazi ◽  
Danni Ramduth ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Disease Progression ◽  
T Cell Responses ◽  
Hla Class I ◽  
Class I ◽  
Effective Control ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Mother And Child

ABSTRACT A broad Gag-specific CD8+ T-cell response is associated with effective control of adult human immunodeficiency virus (HIV) infection. The association of certain HLA class I molecules, such as HLA-B*57, -B*5801, and -B*8101, with immune control is linked to mutations within Gag epitopes presented by these alleles that allow HIV to evade the immune response but that also reduce viral replicative capacity. Transmission of such viruses containing mutations within Gag epitopes results in lower viral loads in adult recipients. In this study of pediatric infection, we tested the hypothesis that children may tend to progress relatively slowly if either they themselves possess one of the protective HLA-B alleles or the mother possesses one of these alleles, thereby transmitting a low-fitness virus to the child. We analyzed HLA type, CD8+ T-cell responses, and viral sequence changes for 61 mother-child pairs from Durban, South Africa, who were monitored from birth. Slow progression was significantly associated with the mother or child possessing one of the protective HLA-B alleles, and more significantly so when the protective allele was not shared by mother and child (P = 0.007). Slow progressors tended to make CD8+ T-cell responses to Gag epitopes presented by the protective HLA-B alleles, in contrast to progressors expressing the same alleles (P = 0.07; Fisher's exact test). Mothers expressing the protective alleles were significantly more likely to transmit escape variants within the Gag epitopes presented by those alleles than mothers not expressing those alleles (75% versus 21%; P = 0.001). Reversion of transmitted escape mutations was observed in all slow-progressing children whose mothers possessed protective HLA-B alleles. These data show that HLA class I alleles influence disease progression in pediatric as well as adult infection, both as a result of the CD8+ T-cell responses generated in the child and through the transmission of low-fitness viruses by the mother.

scholarly journals Relative Dominance of Epitope-Specific Cytotoxic T-Lymphocyte Responses in Human Immunodeficiency Virus Type 1-Infected Persons with Shared HLA Alleles

2001 ◽  
Vol 75 (14) ◽  
pp. 6279-6291 ◽  
Author(s):  
Cheryl L. Day ◽  
Amy K. Shea ◽  
Marcus A. Altfeld ◽  
Douglas P. Olson ◽  
Susan P. Buchbinder ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Hla Class I ◽  
Class I ◽  
Acute Hiv Infection ◽  
Ctl Response ◽  
Immunodeficiency Virus ◽  
Hla Type ◽  
Hiv 1 ◽  
Ctl Responses

ABSTRACT Cytotoxic T lymphocytes (CTL) target multiple epitopes in human immunodeficiency virus (HIV)-infected persons, and are thought to influence the viral set point. The extent to which HLA class I allele expression predicts the epitopes targeted has not been determined, nor have the relative contributions of responses restricted by different class I alleles within a given individual. In this study, we performed a detailed analysis of the CTL response to optimally defined CTL epitopes restricted by HLA class I A and B alleles in individuals who coexpressed HLA A2, A3, and B7. The eight HIV-1-infected subjects studied included two subjects with acute HIV infection, five subjects with chronic HIV infection, and one long-term nonprogressor. Responses were heterogeneous with respect to breadth and magnitude of CTL responses in individuals of the same HLA type. Of the 27 tested epitopes that are presented by A2, A3, and B7, 25 were targeted by at least one person. However, there was wide variation in the number of epitopes targeted, ranging from 2 to 17. The A2-restricted CTL response, which has been most extensively studied in infected persons, was found to be narrowly directed in most individuals, and in no cases was it the dominant contributor to the total HIV-1-specific CTL response. These results indicate that HLA type alone does not predict CTL responses and that numerous potential epitopes may not be targeted by CTL in a given individual. These data also provide a rationale for boosting both the breadth and the magnitude of HIV-1-specific CTL responses by immunotherapy in persons with chronic HIV-1 infection.

scholarly journals HLA Compatibility Requirements for CD8+-T-Cell-Mediated Suppression of Human Immunodeficiency Virus Replication

1998 ◽  
Vol 72 (12) ◽  
pp. 10165-10170 ◽  
Author(s):  
Carl E. Mackewicz ◽  
Marvin R. Garovoy ◽  
Jay A. Levy
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Antiviral Activity ◽  
Hla Class I ◽  
Class Ii ◽  
Class I ◽  
Target Cells ◽  
Hiv Replication ◽  
Immunodeficiency Virus

ABSTRACT CD8+ T cells from human immunodeficiency virus (HIV)-infected individuals can suppress HIV replication in cultured CD4+ cells by a noncytotoxic mechanism. Efficient suppression of HIV replication (>90% reduction) does not require HLA class I or class II histocompatibility between the effector CD8+ T cells and the infected target CD4+ T cells. However, maximal control of HIV production occurs when the CD8+ effector cells and CD4+ target cells are syngeneic. In some cases, more than 20-fold fewer syngeneic CD8+ T cells were required to achieve the same degree of HIV inhibition as HLA-mismatched CD8+ T cells. The increased antiviral activity seen in the syngeneic setting did not map exclusively to either the HLA class I or class II locus. These findings suggest that genetic compatibility (potentially, but not necessarily, at the HLA class I and class II loci) regulates CD8+ T-cell noncytotoxic antiviral activity against infected CD4+ T cells.

scholarly journals Mutually Exclusive T-Cell Receptor Induction and Differential Susceptibility to Human Immunodeficiency Virus Type 1 Mutational Escape Associated with a Two-Amino-Acid Difference between HLA Class I Subtypes

2006 ◽  
Vol 81 (4) ◽  
pp. 1619-1631 ◽  
Author(s):  
Xu G. Yu ◽  
Mathias Lichterfeld ◽  
Senica Chetty ◽  
Katie L. Williams ◽  
Stanley K. Mui ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Hla Class I ◽  
Viral Escape ◽  
Class I ◽  
Immunodeficiency Virus ◽  
Hiv 1

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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