Influence of age and HLA type on interferon‐gamma (IFN‐γ) responses to a naturally occurring polymorphic epitope of Plasmodium falciparum liver stage antigen‐1 (LSA‐1)

• Published in: Clinical and experimental immunology Vol. 122; no. 1; pp. 94 - 100
• Main Authors: Bucci, K., Kastens, W., Hollingdale, M. R., Shankar, A., Alpers, M. P., King, C. L., Kazura, J. W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.10.2000; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Adolescent; Adult; Aging - immunology; Alleles; Animals; Antigenic Variation - genetics; Antigenic Variation - immunology; Antigens, Protozoan - genetics; Antigens, Protozoan - immunology; Biological and medical sciences; Child; Child, Preschool; cytokine; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; g-Interferon; histocompatibility antigen HLA; Histocompatibility Testing; HLA; HLA-A Antigens - genetics; HLA-A Antigens - immunology; HLA-A11 Antigen; HLA-A2 Antigen - immunology; HLA-B Antigens - genetics; HLA-B Antigens - immunology; Human protozoal diseases; Humans; Immunity to Infection; Infectious diseases; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; LSA-1 antigen; LSA‐1; Malaria; Malaria, Falciparum - epidemiology; Malaria, Falciparum - immunology; Malaria, Falciparum - physiopathology; Medical sciences; Middle Aged; Papua New Guinea - epidemiology; Parasitic diseases; Peptides - immunology; Plasmodium falciparum; Plasmodium falciparum - genetics; Plasmodium falciparum - immunology; polymorphism; Protozoal diseases; Tropical medicine; Papua New Guinea; Melanesia; Oceania; Human; Protozoa; HLA-System; Apicomplexa; Protozoal disease; Immune response; Antigenic determinant; Malaria; Liver; Major histocompatibility system; Cytokine; Parasitosis; Infection; Plasmodium falciparum; Immunological investigation; Age; Class I histocompatibility antigen; Gamma interferon; Polymorphism
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2000.01346.x

Antigenic polymorphism and HLA restriction may limit the immunogenicity of a subunit vaccine against liver‐stage Plasmodium falciparum. We examined 59 clinical isolates and five laboratory clones of P. falciparum for polymorphism in the N‐ and C‐terminal regions of LSA‐1, evaluated binding of the corresponding peptides to selected HLA class I alleles, and measured IFN‐γ responses in residents of a malaria‐endemic area of Papua New Guinea where HLA‐A*1101, ‐24, ‐B13, and ‐B40 are the most common class I alleles. LSA‐1 polymorphism was limited to a single non‐synonymous mutation encoding serine (S), proline (P), or threonine (T) at amino acid 85. Nine‐mer 84–92 peptides with S, T, or P at the primary anchor position bound differentially to HLA‐A11, ‐A2, and ‐B7. IFN‐γ ELISPOT responses increased with age in malaria‐exposed subjects: 14–16% and 30–36% of 2–5‐ and 6–54‐year‐olds, respectively, had ≥ 10 IFN‐γ‐secreting cells/106 peripheral blood mononuclear cells when stimulated with at least one peptide variant (P < 0·05). IFN‐γ responses to all three peptides were also greater for older than younger individuals. No children < 3 years old had lymphocytes that responded to all three 84–92 peptides, whereas 45% of adults (mean age 48 years) had aggregated IFN‐γ responses. These data support the notion that age‐related cumulative exposure to P. falciparum increases the frequency of IFN‐γ responses to polymorphic epitopes of liver‐stage antigens such as LSA‐1.