Epitope mapping of human monoclonal antibodies recognizing conformational epitopes within HTLV type 1 gp46, employing HTLV type 1/2 envelope chimeras.
The majority of the antibody response to HTLV-1 surface glycoprotein, gp46, is directed at conformational epitopes. However, the regions of HTLV-1 gp46 that contain conformational epitopes are poorly defined. We previously reported on human monoclonal antibodies (hMAbs) to conformational epitopes within the HTLV-1 surface glycoprotein (gp46) that inhibit HTLV-1-mediated syncytium formation (Hadlock KG, Rowe J, Perkins S, et al.: J Virol 1997;71:5828-5840). To localize the conformational epitopes recognized by these antibodies, chimeric envelope proteins were constructed in which selected regions of the HTLV-1 envelope were replaced with the corresponding sequences from other members of the HTLV family of retroviruses. The chimeras were tested for reactivity with three hMAbs to conformational epitopes in HTLV-1 gp46, PRH-7A, PRH-3, and PRH-4, and one hMAb to a linear epitope, 0.5alpha. hMAb PRH-3 was specifically nonreactive with a chimera that replaced amino acids 32-36 of HTLV-1 gp46 and exhibited sharply reduced reactivity with a chimera that replaced amino acids 224-251 of HTLV-1 with the corresponding HTLV-2 sequence. hMAb PRH-4 was specifically nonreactive with a construct replacing amino acids 1-162 of HTLV-1 gp46 with the corresponding HTLV-2 sequence. Thus, HTLV-1 gp46 contains multiple conformational epitopes located in the amino-terminal portion of the protein.
Hadlock
Kenneth G
KG
Department of Pathology, Stanford University School of Medicine, Stanford, California 94304, USA.
Yang
Qing
Q
Rowe
Judy
J
Foung
Steven K H
SK
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D018604:Epitope Mapping; D005434:Flow Cytometry; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D015367:Human T-lymphotropic virus 2 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011995:Recombination, Genetic; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000276:immunology*; D016415:Sequence Alignment
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015686:Gene Products, env; D015682:Retroviridae Proteins, Oncogenic; C055266:gp46 protein, Human T-cell leukemia virus type I