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Any foreign material—usually of a complex nature and often a protein—that binds specifically to a receptor molecule made by lymphocytes is called an antigen. Antigens include molecules found on invading microorganisms, such as viruses, bacteria, protozoans, and fungi, as well as molecules located on the surface of foreign substances, such as pollen, dust, or transplanted tissue. When an antigen binds to a receptor molecule, it may or may not evoke an immune response. Antigens that induce such a response are called immunogens. Thus, it can be said that all immunogens are antigens, but not all antigens are immunogens. For example, a simple chemical group that can combine with a lymphocyte receptor (i.e., is an antigen) but does not induce an immune response (i.e., is not an immunogen) is called a hapten. Although haptens cannot evoke an immune response by themselves, they can become immunogenic when joined to a larger, more complex molecule such as a protein, a feature that is useful in the study of immune responses.

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Many antigens have a variety of distinct three-dimensional patterns on different areas of their surfaces. Each pattern is called an antigenic determinant, or epitope, and each epitope is capable of reacting with a different lymphocyte receptor. Complex antigens present an ā€œantigenic mosaicā€ and can evoke responses from a variety of specific lymphocytes. Some antigenic determinants are better than others at effecting an immune response, presumably because a greater number of responsive lymphocytes are present. It is possible for two or more different substances to have an epitope in common. In these cases, immune components induced by one antigen are able to react with all other antigens carrying the same epitope. Such antigens are known as cross-reacting antigens.

T cells and B cells differ in the form of the antigen they recognize, and this affects which antigens they can detect. B cells bind to antigen on invaders that are found in circulation outside the cells of the body, while T cells detect only invaders that have somehow entered the cells of the body. Thus foreign materials that have been ingested by cells of the body or microorganisms such as viruses that penetrate cells and multiply within them are out of reach of antibodies but can be eliminated by T cells.