An autologous melanoma cell line selected for loss of expression of the immunodominant MART-1 and gp100 antigens was initially used to carry out a mixed lymphocyte tumor culture (MLTC) in a patient who expressed the human leukocyte antigen (HLA)-AI and HLA-A2 class I major histocompatibility complex alleles. Ten clones identified from this MLTC seemed to recognize melanoma in an HLA-A1-restricted manner but failed to recognize a panel of previously described melanoma antigens. The screening of an autologous melanoma cDNA library with one HLA-Al-restricted melanoma-reactive T-cell clone resulted in the isolation of a cDNA clone called AIM-2 (antigen isolated from immunoselected melanoma-2). The AIM-2 transcript seemed to have retained an intronic sequence based on its alignment with genomic sequences as well as expressed sequence tags. This transcript was not readily detected after Northern blot analysis of melanoma mRNA, indicating that only low levels of this product may be expressed in tumor cells. Quantitative reverse transcriptase-polymerase chain reaction analysis, however, demonstrated a correlation between T-cell recognition and expression in HLA-A1-expressing tumor cell lines. A peptide that was encoded within a short open reading frame of 23 amino acids and conformed to the HLA-A1 binding motif RSDSGQQARY was found to represent the T-cell epitope. The AIM-2-reactive T-cell clone recognized a number of neuroectodermal tumors as well as breast, ovarian, and colon carcinomas that expressed HLA-A1, indicating that this represents a widely expressed tumor antigen. Thus, AIM-2 may represent a potential target for the development of vaccines in patients bearing tumors of a variety of histologies.

Amino Acid Sequence↗

PubMedDate not supplied

Brain interleukin-1 is involved in generation of the serum suppressive factor induced by restraint stress in mice.

Our previous work showed that a factor (a protein with a high molecular weight) in serum was induced by restraint stress in mice and rats, and suppressed lymphocyte proliferation induced by concanavalin A. It was also found that the generation of the serum suppressive factor was under the control of the central nervous system. The present work was designed to investigate the role of interleukin-1 (IL-1) in the brain in the serum suppressive factor. IL-1 receptor antagonist (IL-1ra) was injected intracerebroventricularly in mice and the generation of the serum suppressive factor was found to be significantly decreased in a dose-dependent manner. When the dose of IL-1ra reached 5 micrograms, the generation of the suppressive factor was almost totally abolished. Intracerebroventricular injection of IL-1 beta (1.0 pg) enhanced the generation of the suppressive factor. Taken together, these results indicate the involvement of IL-1 in the brain in mediating generation of the suppressive factor.

Animals↗

PubMedDate not supplied

A factor in lymph node and spleen induced by restraint stress in mice and rats suppresses lymphocyte proliferation.

Extracts from lymph node and spleen in mice and rats subjected to restraint stress significantly suppressed lymphocyte proliferation, but extracts from brain, skeletal muscle, and thymus gland had no effect on lymphocyte proliferation, suggesting that a suppressive factor for lymphocyte proliferation might selectively be induced in lymph node and spleen. Further experiments showed that biochemical properties, molecular weight, correlation between suppressive factors in serum and in extract of the lymph tissue from stressed animals, and control of the generation, all indicated that under the conditions of restraint stress and under the control of central nervous system a suppressive factor was generated in peripheral lymph tissue and then released into the blood-stream, which acted as a strong suppressor of lymphocyte proliferation.

Animals↗

PubMedDate not supplied

[Effect of physiological stimuli on Oddi's sphincter motility].

The myoelectric activity of the sphincter of Oddi was studied both in the fasted and fed states and following administration of gastrointestinal hormones. Electromyographic recordings were obtained from 21 opossums in the fasted state and following administration of 20 Cal/kg of fat, protein, carbohydrate or isocaloric mixture of these three aliments. The proximal segment of the sphincter of Oddi generated spontaneous spike potentials that migrated to the distal segment of the sphincter. The frequency of spike potentials correlated with the migrating myoelectric complex in the duodenum. Following feeding, the migrating myoelectric complex was abolished and substituted by a fed pattern. The duration of the fed pattern and the frequency of spike potentials depended on the kind of aliment. Cholecystokinin and pentagastrin increased and glucagon and secretion decreased the frequency of spike potentials in the sphincter of Oddi. It is concluded from these studies that the sphincter of Oddi may play an important role in controlling the time and rate of biliary drainage into the duodenum.

Action Potentials↗