Antigenicity of Leishmania braziliensis Histone H1 during Cutaneous Leishmaniasis: Localization of Antigenic Determinants

Abstract

The humoral immune response against Leishmania braziliensis histone H1 by patients with cutaneous leishmaniasis is described. For this purpose, the protein was purified as a recombinant protein in a prokaryotic expression system and was assayed by enzyme-linked immunosorbent assay (ELISA) with a collection of sera from patients with cutaneous leishmaniasis and Chagas' disease. The assays showed that L. braziliensis histone H1 was recognized by 66% of the serum samples from patients with leishmaniasis and by 40% of the serum samples from patients with Chagas' disease, indicating that it acts as an immunogen during cutaneous leishmaniasis. In order to locate the linear antigenic determinants of this protein, a collection of synthetic peptides covering the L. braziliensis histone H1sequence was tested by ELISA. The experiments showed that the main antigenic determinant is located in the central region of this protein. Our results show that the recombinant L. braziliensis histone H1 is recognized by a significant percentage of serum samples from patients with cutaneous leishmaniasis, but use of this protein as a tool for the diagnosis of cutaneous leishmaniasis is hampered by the cross-reaction with sera from patients with Chagas' disease.Histones are evolutionarily conserved proteins which associate with DNA to form the chromatin structural unit in eukaryotes, the nucleosome. The name histone H1 is applied to a family of small basic proteins which take part in the stabilization of the nucleosomes and facilitate the assembly of chromatin into higher-order structures. Histone H1 proteins have been described in different trypanosomatids like Crithidia fasciculata (7), Trypanosoma cruzi (1), Trypanosoma brucei (4), Leishmania major (9), and Leishmania braziliensis (13). All of these H1 proteins are smaller than their counterparts from higher eukaryotes due to their lack of a central globular domain. This fact has been related to the imperfect condensation of chromatin in trypanosomatid chromosomes during cell division (8).The first report of the elicitation of a humoral immune response against parasite histones during infection was made in 1995, in which a response against Leishmania infantum H2A during canine visceral leishmaniasis (CVL) was described (16). Similar responses against histone H3, histone H2B, and a fragment of histone H4 from L. infantum were described thereafter (17, 18). The investigators mapped the linear epitopes of histones using synthetic peptides. Their findings led to the conclusion that the humoral response against the L. infantum histones during CVL was triggered by the less conserved regions of the molecule, which correspond to the amino-and carboxy-terminal ends of the protein (15).The term leishmaniasis is applied to a spectrum of diseases caused by different species of the genus Leishmania. This parasite is endemic in 88 countries worldwide, and 350 million people are considered to be at risk of leishmaniasis. Of the 2 million new cases discovered every year, about 1.5 million are cutaneou...

Experimental Validation of Multi-Epitope Peptides Including Promising MHC Class I- and II-Restricted Epitopes of Four Known Leishmania infantum Proteins

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Towards a More Precise Serological Diagnosis of Human Tegumentary Leishmaniasis Using Leishmania Recombinant Proteins

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Identification of novel Leishmania major antigens that elicit IgG2a response in resistant and susceptible mice

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