HLA‐A and HLA‐B in Kenya, Africa:  Allele frequencies and identification of  HLA‐B*1567 and HLA‐B*4426

Luo, Ma; Embreé, Joanne; Ramdahin, S.; Ndinya–Achola, JO; Njenga, Simon; Bwayo, Job; Pan, Shang‐Ling; Mao, Xiaodan; Cheang, Mary; Stuart, T P; Brunham, Robert C.; Plummer, Francis A.

doi:10.1034/j.1399-0039.2002.590503.x

Cited by 30 publications

(34 citation statements)

References 18 publications

(24 reference statements)

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“…The prevalence of blood smears positive for asexual-stage P. falciparum from the 24 asymptomatic adults participating in the current study ranged from 22 to 42% (density, 80 to 13,000 parasites/l) from the three samplings in 2004 and from 25 Table 2). Of the 133 samples with results available for both blood smear and PCR, there was 85% concordance between the two methods: 9 of 133 (7%) positive blood smears were PCR negative, and 11 of 133 (8%) negative blood smears were PCR positive.…”

Section: Msp1mentioning

confidence: 99%

“…PBMC IFN-␥ responses to the MSP1 33 18-mer peptides did not appear to be stable, due to the relatively low frequency of responders and low magnitude of IFN-␥ responses measured by ELISPOT. There were only two individuals who consistently responded to a single peptide, suggesting that overcoming HLA haplotype restriction might improve responses; however, HLA matching a vaccine to individuals would be logistically impossible and prohibitively expensive due to the extreme HLA heterogeneity in African populations (25). In this study, we were not able to determine the HLA class I and II genotypes of the study participants, results which would have allowed us to evaluate the influence of HLA restriction on the stability of IFN-␥-specific peptide responses.…”

Section: Downloaded Frommentioning

confidence: 99%

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Allele Specificity of Gamma Interferon Responses to the Carboxyl-Terminal Region of Plasmodium falciparum Merozoite Surface Protein 1 by Kenyan Adults with Naturally Acquired Immunity to Malaria

et al. 2010

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Cross-sectional seroepidemiological studies of populations naturally exposed to Plasmodium falciparum suggest an association between protection from malaria and circulating antibodies to the carboxyl terminus of merozoite surface protein 1 (MSP1) Infection with Plasmodium spp., the protozoan parasites responsible for malaria, results in an estimated 350 to 500 million infections per year with an ensuing 1 to 2 million deaths, the majority of which are caused by Plasmodium falciparum (45). Adults who have maintained lifelong residence in areas where malaria transmission is stable and of high intensity gradually develop naturally acquired immunity, an age-related phenomenon marked by a reduced frequency and severity of clinical malaria and high-density blood stage parasitemia relative to that of infants and children. Maintaining naturally acquired immunity is thought to require continuing exposure to malaria blood stage antigens mediated through asymptomatic low-density blood stage infection. A malaria vaccine that would accelerate the development of naturally acquired immunity during infancy and childhood has been a high priority for many years. The recent success of vector interventions, such as insecticidetreated bed nets, in decreasing transmission of P. falciparum in sub-Saharan Africa suggests that a blood stage vaccine would also be desirable in order to maintain the strength and duration of naturally acquired immunity among adults (17)..Merozoite surface protein 1 (MSP1) is one of several candidates that have been considered for a blood stage vaccine. The primary ϳ195-kDa MSP1 protein is expressed during schizogony and is processed initially to form a 42-kDa carboxyl-terminal fragment (MSP1 42 ) that remains attached to the merozoite surface. A second proteolytic cleavage results in the shedding of a 33-kDa fragment (MSP1 33 ) with formation of a 19-kDa carboxyl-terminal fragment (MSP1 19 ) anchored to the merozoite surface during invasion of the red blood cell (RBC) (4, 5). The 19-kDa fragment of MSP1 contains the major B-cell epitopes (18), the recognition of which is enhanced by T-helper epitopes in the 33-kDa fragment (1). Antibodies to MSP1 19

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Section: Msp1mentioning

confidence: 99%

Section: Downloaded Frommentioning

confidence: 99%

Allele Specificity of Gamma Interferon Responses to the Carboxyl-Terminal Region of Plasmodium falciparum Merozoite Surface Protein 1 by Kenyan Adults with Naturally Acquired Immunity to Malaria

et al. 2010

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“…A number of studies have characterized HLA types within and between West African, South African (50), and East African populations (51). Focusing on the HLA-B locus, a number of typically African alleles such as HLA-B53 are seen across the populations at high frequencies, whereas other alleles vary in frequency depending on location.…”

Section: Figure 7 (A) Ifn-g Cd8mentioning

confidence: 99%

Assessment of Immune Interference, Antagonism, and Diversion following Human Immunization with Biallelic Blood-Stage Malaria Viral-Vectored Vaccines and Controlled Malaria Infection

Elias

Collins

Halstead

et al. 2013

The Journal of Immunology

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Overcoming antigenic variation is one of the major challenges in the development of an effective vaccine against Plasmodium falciparum, a causative agent of human malaria. Inclusion of multiple antigen variants in subunit vaccine candidates is one strategy that has aimed to overcome this problem for the leading blood-stage malaria vaccine targets, merozoite surface protein 1 (MSP1) and apical membrane antigen 1 (AMA1). However previous studies, utilizing malaria antigens, have concluded that inclusion of multiple allelic variants, encoding altered peptide ligands (APL), in such a vaccine may be detrimental to both the priming and in vivo re-stimulation of antigen-experienced T cells. Here we analyze the T cell responses to two alleles of MSP1 and AMA1 induced by vaccination of malaria-naïve adult volunteers with bi-valent viral vectored vaccine candidates. We show a significant bias to the 3D7/MAD20 allele compared to the Wellcome allele for the 33kDa region of MSP1, but not for the 19kDa fragment or the AMA1 antigen. Whilst this bias could be caused by ‘immune interference’ at priming, the data don’t support a significant role for ‘immune antagonism’ during memory T cell re-stimulation, despite observation of the latter at a minimal epitope level in vitro. A lack of class I HLA epitopes in the Wellcome allele that are recognized by vaccinated volunteers may in fact contribute to the observed bias. We also show that controlled infection with 3D7 strain P. falciparum parasites neither boosts existing 3D7-specific T cell responses nor appears to ‘immune divert’ cellular responses towards the Wellcome allele.

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“…For 24 patients, high-resolution HLA typing was obtained for the HLA loci A and B (22,26). For one patient (patient code 2866), only low-resolution typing was available for loci A and B.…”

Section: Hla Genotypingmentioning

confidence: 99%

Interdisciplinary Analysis of HIV-Specific CD8+ T Cell Responses against Variant Epitopes Reveals Restricted TCR Promiscuity

Hoof

Pérez

Buggert

et al. 2010

The Journal of Immunology

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HIV-1–specific CTL responses play a key role in limiting viral replication. CTL responses are sensitive to viral escape mutations, which influence recognition of the virus. Although CTLs have been shown to recognize epitope variants, the extent of this cross-reactivity has not been quantitatively investigated in a genetically diverse cohort of HIV-1–infected patients. Using a novel bioinformatic binding prediction method, we aimed to explain the pattern of epitope-specific CTL responses based on the patients’ HLA genotype and autologous virus sequence quantitatively. Sequences covering predicted and tested HLA class I-restricted epitopes (peptides) within the HIV-Gag, Pol, and Nef regions were obtained from 26 study subjects resulting in 1492 patient-specific peptide pairs. Epitopes that were recognized in ELISPOT assays were found to be significantly more similar to the autologous virus than those that did not elicit a response. A single substitution in the presented epitope decreased the chance of a CTL response by 40%. The impact of sequence similarity on cross-recognition was confirmed by testing immune responses against multiple variants of six selected epitopes. Substitutions at central positions in the epitope were particularly likely to result in abrogation of recognition. In summary, the presented data demonstrate a highly restricted promiscuity of HIV-1–specific CTL in the recognition of variant epitopes. In addition, our results illustrate that bioinformatic prediction methods are useful to study the complex pattern of CTL responses exhibited by an HIV-1–infected patient cohort and for identification of optimal targets for novel therapeutic or vaccine approaches.

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HLA‐A and HLA‐B in Kenya, Africa:  Allele frequencies and identification of  HLA‐B1567 and HLA‐B4426

Cited by 30 publications

References 18 publications

Allele Specificity of Gamma Interferon Responses to the Carboxyl-Terminal Region of Plasmodium falciparum Merozoite Surface Protein 1 by Kenyan Adults with Naturally Acquired Immunity to Malaria

Allele Specificity of Gamma Interferon Responses to the Carboxyl-Terminal Region of Plasmodium falciparum Merozoite Surface Protein 1 by Kenyan Adults with Naturally Acquired Immunity to Malaria

Assessment of Immune Interference, Antagonism, and Diversion following Human Immunization with Biallelic Blood-Stage Malaria Viral-Vectored Vaccines and Controlled Malaria Infection

Interdisciplinary Analysis of HIV-Specific CD8+ T Cell Responses against Variant Epitopes Reveals Restricted TCR Promiscuity

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HLA‐A and HLA‐B in Kenya, Africa: Allele frequencies and identification of HLA‐B*1567 and HLA‐B*4426

Cited by 30 publications

References 18 publications

Allele Specificity of Gamma Interferon Responses to the Carboxyl-Terminal Region of Plasmodium falciparum Merozoite Surface Protein 1 by Kenyan Adults with Naturally Acquired Immunity to Malaria

Allele Specificity of Gamma Interferon Responses to the Carboxyl-Terminal Region of Plasmodium falciparum Merozoite Surface Protein 1 by Kenyan Adults with Naturally Acquired Immunity to Malaria

Assessment of Immune Interference, Antagonism, and Diversion following Human Immunization with Biallelic Blood-Stage Malaria Viral-Vectored Vaccines and Controlled Malaria Infection

Interdisciplinary Analysis of HIV-Specific CD8+ T Cell Responses against Variant Epitopes Reveals Restricted TCR Promiscuity

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HLA‐A and HLA‐B in Kenya, Africa:  Allele frequencies and identification of  HLA‐B1567 and HLA‐B4426